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Question

Six months after her original diagnosis, Mrs X (80 y/o, diagnosed with chronic heart failure) visits her GP because she still gets very short of breath, especially when she lies down. Her current medications include enalapril, atenolol, zopiclone, aspirin and furosemide. What additional treatment should the doctor prescribe her? ``` A. Angiotensin II receptor antagonist B. Angiotensin-converting enzyme inhibitors C. Amlodipine D. β-Blockers E. Brain-type natriuretic peptide F. Digoxin G. Lipid profile H. Loop diuretics I. Myoglobin J. Potassium-sparing diuretics K. Spironolactone L. Thiazide diuretics M. Thyroid function tests N. Transoesophageal echocardiography O. Transthoracic Doppler echocardiography P. Troponin I ```

Answer 1

K – Spironolactone Spironolactone is an aldosterone antagonist; therefore it causes increased sodium secretion and reduced potassium excretion. Because it does not cause hypokalaemia (unlike the thiazide and loop diuretics), spironolactone is known as a potassium-sparing diuretic. Amiloride is another example of such a drug. Spironolactone is indicated in patients with severe symptomatic disease that is not controlled by optimal medical therapy to improve symptoms and mortality. Since this medication reduces potassium excretion by the kidneys, it should not be given to patients with a potassium level over 5.0 mmol/L or to patients taking potassium supplements. Patients should have their serum potassium measured prior to prescription and at regular intervals thereafter in order to detect hyperkalaemia. Other well-known side-effects of spironolactone include hyponatraemia, gynaecomastia and menstrual disturbance.

Answer 2

C – Diabetic dermopathy Diabetic dermopathy describes the presence of depressed pigmented scars in the shin. It is associated with diabetic microangiopathy. Other skin features of diabetes include necrobiosis lipoidica diabeticorum (shiny, atrophic, yellowish-red plaques on the shins), cheiroarthropathy (a sclerodermalike thickening of the skin of the hands), granuloma annulare (small, papular lesions arranged in a ring and found on the back of the hands or feet) and acanthosis nigricans.

Answer 3

E – Erythema ab igne Erythema ab igne is a brown lacy rash seen on skin that has been exposed to heat for long periods of time. It classically develops in hypothyroid patients who are cold and spend a lot of time in front of the fire. Excessive hot water bottle use can also result in the rash. Other cutaneous features of hypothyroidism include alopecia (especially loss of the outer third of the eyebrows), dry coarse hair, puffy yellow skin, periorbital oedema, xanthomas and a malar flush on an otherwise pale face (‘strawberries and cream’ appearance).

Answer 4

J – U-waves The 4-day history of diarrhoea and vomiting followed by the development of severe muscle weakness and cramps suggests hypokalaemia secondary to excessive gastrointestinal potassium loss. Other causes of reduced total body potassium include diuretic use, Conn’s syndrome, excessive sweating and burns. Potassium can also be redistributed from the extracellular compartment into the intracellular compartment, resulting in a reduction in bioavailable potassium despite there being normal total body potassium levels. Causes of potassium redistribution include β2-antagonist use (e.g. salbutamol), excess insulin administration and alkalosis. The clinical features of hypokalaemia become evident with serum potassium levels less than 2.5 mmol/L. These include lethargy, polyuria, profound muscle weakness, muscle cramps, palpitations and arrhythmia. ECG changes in hypokalaemia include U-wave formation (upward deflections following the T-waves), flattened T-waves, ST-segment depression, and atrial and ventricular arrhythmias. Treatment of hypokalaemia involves correcting the underlying cause and replacing the lost potassium. Patients with potassium levels above 2.5 mmol/L can usually be managed with oral potassium supplements.

Answer 5

F – J-waves This patient is hypothermic secondary to prolonged environmental exposure. Severe hypothermia can lead to coagulopathy, bradycardia, heart failure, arrhythmia and death. The ECG in severely affected patients may show an upward deflection following the R-wave of the QRS complex (J-wave). Patients with hypothermia should be re-warmed slowly at a rate no greater than 0.5°C/h, as rapid re-warming can cause vasodilatation, hypotension and circulatory collapse. Methods of re-warming include removal of wet clothing, supplying warmed humidified oxygen, applying a bear hugger device and infusing warm saline intravenously. More invasive methods of re-warming include peritoneal, pleural and bladder lavage with warmed fluid. Due to the risk of arrhythmia, hypothermic patients should be managed on a cardiac and blood pressure monitor.

Answer 6

G – Hepatitis B surface antigen (HBsAg) If HBsAg is still detected in the serum 6 months after an acute HBV infection, the patient has become a chronic carrier of the virus. The risk of developing chronic HBV infection is related to age at the time of infection. The majority of infected neonates develop chronic infection, whereas only 5–10% of adults do so. Patients with chronic hepatitis B are at risk of developing cirrhosis, liver failure and hepatocellular carcinoma. The treatment of chronic hepatitis B can involve interferon-α, peginterferon-α2a, lamivudine and (in some patients) eventual liver transplantation.

Answer 7

E – Hepatitis B e antigen (HBeAg) HBeAg can be present in both acute and chronic hepatitis B and indicates a high level of infectivity. The presence of HBeAg in chronic hepatitis B suggests that the patient is infective and has an aggressive disease requiring treatment. In addition to establishing infectivity, measurement of HBeAg can be used to assess the efficacy of treatment, with falling levels indicating success. It should be noted that there are some mutant strains of HBV found in Asia and the Middle East that do not produce HBeAg. HBV DNA levels can also be used to assess disease activity, with high levels indicating active disease and infectivity.

Answer 8

C – Hepatitis B core antibody (HBcAb) HBcAb can be present in acute and chronic infection. They are formed against the HBcAg, which is found only within the liver and therefore cannot be detected using serology. In acute infection, it is the second marker to be detected, after HBsAb, and is usually seen after 4 weeks of infection. In chronic disease, the presence of high titres of HBcAb, in the absence of HBeAg, indicates low infectivity and disease activity. This serological picture is associated with a better prognosis, with fewer individuals progressing to cirrhosis and hepatocellular carcinoma.

Answer 9

M – Trigeminal neuralgia Trigeminal neuralgia describes sharp, stabbing pains in the second and third divisions of the trigeminal nerve. The pain is severe, brief and repetitive, often causing the patient to flinch. (This feature gives rise to the French name for the condition ‘tic douloureux’ – painful twitch). The pain may often have triggers, such as touching or eating. Trigeminal neuralgia is most common in older women, and the condition has a tendency to improve and relapse. The underlying cause may be compression of the trigeminal nerve rootlets at their entry into the brain stem by aberrant loops of cerebellar arteries. Management options include carbamazepine, phenytoin or gabapentin, which can improve the neuropathic pain.

Answer 10

J – Unilateral recurrent laryngeal nerve palsy The recurrent laryngeal nerve can be damaged during thyroidectomy via a number of mechanisms, including transection, infarction, diathermy burns and accidental ligation. Unilateral recurrent laryngeal nerve injury usually presents in the days following surgery with a hoarse voice and dyspnoea. In some cases, the symptoms will disappear after a few months. For those who do not recover, a number of surgical interventions are available. In total thyroidectomy, both laryngeal nerves can be damaged. This is a potentially life-threatening complication, since both vocal cords are paralysed, resulting in upper airway obstruction at extubation. If this is the case, the patient should be re-intubated and have their neck explored to assess the extent of any damage. If extubation continues to fail, the patient will require a tracheostomy. In the long term, surgical correction may allow the airway to be maintained without tracheostomy, but the voice will not recover.

Answer 11

G – Escherichia coli cystitis Cystitis usually presents with dysuria, frequency of urine, suprapubic discomfort and fever. Cystitis is much more common in women than in men due to the shorter urethra in women. Escherichia coli, usually found in the bowel, is the most common pathogen responsible for uncomplicated cystitis in the UK. Cystitis can be confirmed by the presence of leucocytes, nitrites and blood in the urine. A midstream urine (MSU) sample should be sent to microbiology for microscopy, culture and sensitivity. A positive culture is when more than 105 of a single organism are grown per millilitre of urine. The growth of mixed bacterial species usually indicates contamination of the sample. Antibiotic treatment should be guided by local patterns of bacterial resistance and MSU sensitivity results. Uncomplicated cystitis is usually treated with a 3- to 5-day course of trimethoprim. Other antibiotics that are used to treat cystitis include amoxicillin, ciprofloxacin, cefradine and nitrofurantoin. Patients who are susceptible to recurrent urinary tract infection can be prescribed prophylactic antibiotics (e.g. 100 mg of trimethoprim once nightly). Patients should be advised to drink lots of fluids and avoid dehydration. Urinary tract infections in men and children require further investigation

Answer 12

I – Proteus mirabilis urinary tract infection Proteus mirabilis is a Gram-negative anaerobic pathogen that can cause urinary tract infection. In addition, P. mirabilis infection causes the urine to become more alkaline, which predisposes to the development of urinary calculi. P. mirabilis infection is more common in patients with structural abnormalities of their urinary tract and in patients with long-term catheters.

Answer 13

F – Intravenous insulin with fluid resuscitation This patient has entered a hyperosmolar non-ketotic state (HONK). HONK is seen in people with type 2 diabetes, including previously undiagnosed patients. The event is usually triggered by an underlying illness, the ingestion of a high sugar load or the use of medications that cause a rise in plasma glucose (e.g. steroids). Patients usually present in a confused state, with a history of polyuria and polydipsia. The patient has a high plasma glucose, which can be in excess of 30 mmol/L. In HONK, the circulating insulin is sufficient to prevent ketogenesis but insufficient to allow the peripheral uptake and metabolism of glucose. Therefore the patient does not become acidotic. The hyperglycaemia causes an osmotic diuresis that rapidly dehydrates the patient and produces an extremely high plasma osmolality. HONK is treated with a combination of intravenous fluid resuscitation and intravenous insulin. Care must be taken not to reduce the glucose levels or sodium concentration too rapidly, as the resultant osmotic shifts can result in fatal cerebral oedema. The insulin should therefore be started at a low rate (e.g. 3 units/h) and only isotonic (0.9%) saline should be prescribed. HONK also places the patient at high risk of thromboembolic events such as deep vein thrombosis, pulmonary embolism and stroke; therefore all patients should receive prophylactic heparin. The mortality rate of HONK approaches 30%, which is likely to be a reflection of the advanced age of many of the patients and the presence of underlying illness.

Answer 14

B – Increase insulin dose temporarily Although this case does not represent a true diabetic emergency, the patient is at risk of deteriorating. As discussed above in Case 1, in the presence of illness, the patient’s insulin requirements increase even if they are not eating. If the insulin dose is lowered or remains the same, the patient may become ketoacidotic. The patient in this scenario should therefore be advised to increase his insulin dose temporarily and seek medical attention. Regular capillary blood glucose measurement is essential until an improvement is seen.

Answer 15

F – Cryptogenic fibrosing alveolitis Cryptogenic fibrosing alveolitis (CFA) is a fibrosing alveolitis that is not associated with another disease. It is most common in older male smokers. CFA presents with exertional dyspnoea and a dry cough. Examination may reveal clubbing and bilateral end-inspiratory crepitations, especially at the lower zones. As disease progresses, central cyanosis and cor pulmonale develop. Chest X-ray demonstrates diffuse pulmonary opacities, or honeycombing in advanced disease. Pulmonary function tests show a restrictive defect (with a reduced vital capacity and reduced forced expiratory volume). The diagnosis is confirmed with high-resolution CT. Treatment is with prednisolone and azathioprine, although CFA tends to respond poorly. Death usually occurs within 5 years of diagnosis.

Answer 16

G – Extrinsic allergic alveolitis Extrinsic allergic alveolitis is caused by the inhalation of organic dusts, resulting in an immune complex-mediated reaction with the formation of granulomas within the lung (and eventual lung fibrosis). Patients present with fever, muscle aches, cough, dyspnoea (no wheeze) and headaches. Examination reveals widespread end-inspiratory crepitations. Chest X-ray demonstrates micronodular shadowing, especially in the upper zones. Lung function tests confirm a restrictive defect. The diagnosis of extrinsic allergic alveolitis is made by demonstrating typical clinical and radiological features along with identifying the underlying allergen. Treatment is with prednisolone and requires avoidance of the precipitating allergen. Examples of allergens that cause extrinsic allergic alveolitis include: * farmer’s lung: Aspergillus fumigatus in mouldy hay * bird fancier’s lung: avium serum proteins found in bird droppings and feathers * malt worker’s lung: A. clavatus in mouldy maltings.

Answer 17

C – Chancroid Chancroid is caused by the Gram-negative bacterium Haemophilus ducreyi, and is found mostly in tropical countries. It is an ulcerative condition of the genitalia that develops within a week of exposure. Lesions begin as a small papule, which eventually ulcerates to form single or multiple, painful, superficial ulcers. Inflammation may lead to phimosis. Enlargement and suppuration of inguinal lymph nodes may occur, leading to a unilocular abscess (bubo) that can rupture to form a discharging sinus. Treatment is with appropriate antibiotics (e.g. erythromycin).

Answer 18

D – Chlamydia infection The right upper quadrant pain with non-specific urethritis in a girl with this history suggests chlamydial infection. Chlamydia infection is caused by the oculogenital serovars D–K of Chlamydia trachomatis. Infection tends to be asymptomatic, although there can be increased vaginal discharge, dysuria and urinary frequency. Ascending infection can cause salpingitis and, if it enters the abdominal cavity, perihepatitis (Fitz-Hugh–Curtis syndrome), which leads to right upper quadrant pain and tenderness. Chlamydia infection is a major cause of infertility and increases the possibility of a future ectopic pregnancy. In males, symptoms include mucopurulent discharge and dysuria, although it is asymptomatic in 25%. Epididymo-orchitis is a complication. Diagnosis of chlamydial infection is by urine antigen detection or vaginal swab culture. Treatment is with doxycycline. Acute pelvic inflammatory disease is characterized by pelvic pain, pyrexia, cervical excitation, adnexal tenderness and a raised white cell count. It is most often caused by chlamydia infection and gonorrhoea.

Answer 19

F – Pseudogout Calcium pyrophosphate deposition disease is caused by the deposition of calcium pyrophosphate dihydrate crystals in the joints. The crystals deposit along the cartilages, producing a linear chondrocalcinosis that is best seen on the meniscus on X-ray. Shedding of crystals into the joint precipitates an acute synovitis known as pseudogout. Patients present with acute-onset pain, swelling and redness in the affected joint. Pseudogout is most common in elderly women and usually affects the knee or wrist. The diagnosis is made by joint aspiration, demonstrating the weakly positively birefringent brick-shaped crystals of calcium pyrophosphate. The joint fluid should always be sent for culture to exclude a septic arthritis. The treatment of pseudogout is with nonsteroidal anti-inflammatory drugs (NSAIDs). The chondrocalcinosis itself cannot be treated.

Answer 20

H – Reiter’s syndrome The triad of arthritis, urethritis and iritis is indicative of Reiter’s syndrome.

Answer 21

M – Spinal muscular atrophy Spinal muscular atrophy describes a group of genetic disorders affecting spinal and cranial motor neurons. There is degeneration of anterior horn cells, resulting in progressive proximal and distal weakness, wasting, and fasciculation (usually symmetrical). An example is Werdnig–Hoffmann disease: autosomal recessive severe muscle weakness, with death occurring by 12 months. Spinal muscular atrophy is the second most common cause of neuromuscular disease in the UK

Answer 22

I - Muscular Dystrophy Muscular dystrophy describes a group of inherited disorders with progressive degeneration of groups of muscles without involvement of the nervous system. It is characterized by symmetrical wasting and weakness, with no fasciculations or sensory loss. The most common muscular dystrophy is the Duchenne type, an X-linked recessive deficiency of the protein dystrophin, which is required to maintain the integrity of muscle cell walls. Duchenne muscular dystrophy begins in childhood and affects the proximal arms and legs. There is pseudohypertrophy of the calves (due to replacement of muscle by fibrosis and fat), a waddling gait and difficultly standing (children may ‘climb’ up their legs to help stand up – Gower’s sign). Death by respiratory failure or cardiomyopathy occurs in the early 20s. A diagnosis of muscular dystrophy is confirmed by electromyography and biopsy. Creatine kinase may also be elevated. Management of muscular dystrophy is supportive. Other forms of muscular dystrophy include Becker muscular dystrophy (Xlinked recessive, with features similar to Duchenne muscular dystrophy but less severe, and with death occurring by the early 40s), myotonic dystrophy (autosomal dominant, weakness of temporal, facial, sternomastoid and distal limb muscles), fascioscapulohumeral dystrophy (autosomal dominant, affecting facial and shoulder girdle muscles) and limb girdle dystrophy (autosomal recessive, affecting pelvic and shoulder girdles).

Answer 23

F – Mononeuritis multiplex Mononeuritis multiplex is a form of peripheral neuropathy where there is damage to at least two anatomically distinct peripheral or spinal nerves. There may be a variety of underlying pathologies, such as ischaemia or inflammation of the nerves. Common causes of mononeuritis multiplex include diabetes mellitus, polyarteritis nodosa, rheumatoid arthritis and systemic lupus erythematosus.

Answer 24

A – Background retinopathy Diabetic eye disease is a serious microvascular complication of diabetes, and is the leading cause of blindness in the under-60 age group in the developed world. Background retinopathy is asymptomatic and is usually detected during the screening of diabetic patients. The pathological processes leading to retinopathy relate to increased retinal arterial blood flow secondary to hyperglycaemia, which results in the formation of microaneurysms, increased capillary permeability and retinal ischaemia. The pathognomonic changes of background retinopathy are blot haemorrhages, capillary microaneurysms (dots) and hard exudates, which appear as yellow plaques and contain lipid deposits. If a patient is shown to have background retinopathy, they must receive annual fundoscopy or diabetic photography to assess disease progression. If there is concern that disease is progressing, the patient should be reviewed again after 3 months. Each patient must undergo a holistic review of their glycaemic control, blood pressure, lipid profile and lifestyle. If the glycaemic control, hypertension and hyperlipidaemia are not corrected, the background retinopathy can progress to pre-proliferative and proliferative retinopathy, which is associated with a significant risk of blindness, vitreous haemorrhage and retinal detachment.

Answer 25

F – Macular oedema Diabetic maculopathy is most commonly seen in older patients with type 2 diabetes and is the leading cause of blindness in this group. Macular oedema cannot be seen on fundoscopy, but must always be suspected if the patient complains of deteriorating vision or if there is objective evidence of deteriorating visual acuity (i.e. using a Snellen chart). In addition to macular oedema, the macula can be affected by retinopathy, including the presence of haemorrhages, exudates and neovascularization. If maculopathy is suspected, the patient should be referred to an ophthalmologist for assessment and possible retinal photocoagulation therapy.

Answer 26

I – Retinal detachment Retinal detachment occurs when the outer pigment epithelium detaches from the inner retina, which contains the neurons. In patients with proliferative retinopathy, the retina detaches as a result of traction caused by the formation and deposition of fibrous bands. Patients complain of visual floaters, reduced visual acuity and visual field loss (often described as a curtain passing across their visual field). If the macula becomes detached, which usually occurs when the upper half of the retina detaches, the patient will suffer permanent damage to their central vision. On fundoscopy, the retina often appears grey and lifeless and bulges forward. If retinal detachment is suspected, the patient should be referred for urgent ophthalmological review.

Answer 27

B – Acute mitral valve regurgitation Acute mitral regurgitation is usually seen 2–10 days after an inferior myocardial infarction (MI) and is often fatal. It is usually secondary to rupture of a papillary muscle or the chordae tendineae. It presents with symptoms and signs of acute left ventricular failure, including shortness of breath and the production of pink frothy sputum. On auscultation, there is a loud pansystolic murmur best herd at the apex that radiates into the axilla. The patient is usually haemodynamically compromised, with severe hypotension, low oxygen saturation and poor urine output. If the patient survives the initial period, a surgical opinion should be sought regarding possible repair/valve replacement.

Answer 28

F – Cardiac tamponade In cardiac tamponade, there is rapid accumulation of fluid within the pericardial space, which compresses the heart, causing pump failure and cardiogenic shock. The patient is usually hypotensive, with distended neck veins and quiet heart sounds – features described by Beck’s triad (not to be confused with Beck’s cognitive triad: negative view of oneself, negative interpretation of past experiences and negative expectation of the future). Cardiac tamponade can be confirmed by echocardiography, but the rapidly fatal cardiogenic shock usually necessitates a clinical diagnosis and immediate treatment with pericardial aspiration by pericardiocentesis.

Answer 29

I – Pyogenic granuloma A pyogenic granuloma is an acquired haemangioma (note that it is neither pyogenic nor a granuloma!) that occurs most often on the head, trunk, hands and feet. It develops at a site of trauma (e.g. a thorn prick) as a bright-red nodule that bleeds easily and enlarges rapidly over 2–3 weeks. It affects the young and old extremes of age, but is most common in pregnant women. These lesions are benign and are managed by excision, although smaller lesions may resolve spontaneously.

Answer 30

G – Ramsay Hunt syndrome Ramsay Hunt syndrome is caused by herpes zoster infection of the geniculate ganglion, affecting the facial nerve and sometimes the vestibulocochlear nerve, which is in close proximity. Features include paralysis of the facial muscles on the affected side, with a herpetic eruption on the ear canal. Patients may also suffer with tinnitus, hearing loss and vertigo. Oral aciclovir improves the prognosis and reduces the risk of post-herpetic neuralgia.

Answer 31

D – Labyrinthitis Labyrinthitis (also known as vestibular neuronitis) is the most common cause of vertigo, and may be viral in origin. Patients present with explosive severe vertigo, vomiting and ataxia (without tinnitus and deafness). Symptoms settle down over a few days. Management is with antiemetics, often prochlorperazine.

Answer 32

A – Ankylosing spondylitis Ankylosing spondylitis (AS) is an inflammatory disorder of the back that is more common in males. Patients present with insidious-onset lower back pain and stiffness that is worse in the morning and gets better with exercise. There is poor spinal flexion, and in severe cases patients develop a rigid lower spine with a hunch (known as the ‘question mark posture’ or ‘hang dog posture’). AS may also affect the large joints asymmetrically. AS is associated with a number of extra-articular features, which are remembered by the ‘five As’: Apical lung fibrosis, Anterior uveitis, Achilles’ tendonitis/plantar fasciitis, Aortic regurgitation and Amyloidosis. This diagnosis of AS is made using Schober’s test: two fingers are placed 10 cm apart on the lower back of the patient (5 cm above and below the L5 vertebra in the midline), and the patient is asked to flex. An increase between the fingers of <5 cm indicates spinal stiffness. X-ray of the hip shows blurred margins of the sacroiliac joints (sacroiliitis). Characteristic radiological features of the spine in AS include erosion of the corners of the vertebral bodies (Romanus lesions), the development of bony spurs (syndesmophytes) and calcification of the spinal ligaments (bamboo spine). Treatment options in AS are physiotherapy, exercise and slow-release NSAIDs, e.g. indometacin. Most patients manage to lead a normal life, although severe cases may impair ventilation. AS is an example of a seronegative spondyloarthropathy, i.e. a disease associated with HLA-B27 that is characterized by a lack of rheumatoid factor (hence ‘seronegative’). Other spondyloarthropathies are psoriatic arthritis, Reiter’s disease and enteropathic arthritis.

Answer 33

K – Still’s disease Juvenile idiopathic arthritis (JIA) was previously referred to as juvenile chronic arthritis or juvenile rheumatoid arthritis. JIA is defined as joint inflammation persisting for 6 weeks or more, with initial onset in a person under 16 years of age, in the absence of another specific cause. Pauciarticular JIA usually occurs in younger children, affecting the knees, ankles and wrists most commonly. Polyarticular JIA is more common in girls of all ages, usually symmetrically involving the hands and wrists. Complications of JIA include chronic anterior uveitis, flexion contraction of the joints and amyloidosis. Still’s disease is a systemic form of juvenile arthritis that is thought to be an autoimmune disorder. It usually begins at the age of 3–4 years and is more common in girls. Features of Still’s disease include intermittent high pyrexia and a salmon-pink rash, with aches and pains of the joints and muscles. Other features are hepatosplenomegaly, lymphadenopathy and pericarditis. Inflammatory markers such as C-reactive protein are raised; however, antinuclear antibody and rheumatoid factor are usually negative. Management options include physiotherapy, resting splints, NSAIDs, disease-modifying drugs (e.g. methotrexate and ciclosporin) and steroids. The younger the age of onset of Still’s disease, the worse the prognosis.

Answer 34

H – Reye’s syndrome Reye’s syndrome is associated with aspirin use in children, and causes fatty infiltration of the liver and severe encephalopathy. Children can initially present with a mild illness, but often progress to coma. Treatment is directed at managing complications such as raised intracranial pressure and hypoglycaemia. This condition is fatal in up to 40% of cases. For this reason, aspirin should never be given to children.

Answer 35

K – Pneumonia Pneumonia is an acute respiratory illness with recent radiological pulmonary shadowing. A chest infection without chest X-ray changes is known as a lower respiratory tract infection. Community-acquired pneumonias are spread by droplet inhalation, and present with cough, fever and pleuritic chest pain. Cough is initially dry, but later becomes productive and may be blood stained. Examination reveals bronchial breath sounds in the affected area (due to consolidation) and coarse crepitations. Severity of pneumonia is assessed using the CURB-65 score. The most common pathogens involved in community-acquired pneumonia are Streptococcus pneumoniae (30%), Mycoplasma pneumoniae, Staphylococcus aureus and Chlamydophila pneumoniae (previously known as Chlamydia pneumoniae). The resulting infection may be lobar pneumonia (homogeneous consolidation of one or more lobes) or bronchopneumonia (patchy alveolar consolidation that commonly affects both lower lobes). Investigations include chest X-ray and sputum culture. Treatment is with relevant antibiotics. Empirical regimens include oral amoxicillin for uncomplicated cases and intravenous clarithromycin plus co-amoxiclav for severe disease. Seven to ten days of treatment is normally sufficient.

Answer 36

I – Renal biopsy Deteriorating renal function in a patient with a transplanted kidney should always be taken seriously, as there is a possibility of organ rejection. Other causes include vessel thrombosis, infection and recurrence of existing disease, e.g. immunoglobulin A (IgA) nephropathy. A percutaneous renal biopsy will reveal the presence, aetiology and severity of any rejection process. Acute rejection is usually treated with pulsed steroid therapy (methylprednisolone). In severe episodes of rejection, antithymocyte globulin, which destroys T lymphocytes, can be given to slow the rejection process. Chronic rejection is often due to the fibrosis of the microcirculation within the graft and is usually irreversible. Chronic rejection usually means that the patient is re-listed for transplantation.

Answer 37

H – Iron-deficiency anaemia secondary to gastrointestinal bleeding Iron-deficiency anaemia (IDA) is defined as a haemoglobin concentration below 13.5 g/dL in males or 11.5 g/dL in females, in association with a low MCV and evidence of depleted iron stores (i.e. a low ferritin and a raised total ironbinding capacity). In the developed world, IDA is usually secondary to chronic blood loss from gastrointestinal, uterine and urinary tract sources. (Worldwide, hookworm infection and schistosomiasis are common causes.) In cases where the source of bleeding is obvious, further investigation is usually not necessary and treatment can begin. However, in many instances, bleeding goes unnoticed and is secondary to a more sinister cause such as gastrointestinal malignancy. Therefore, patients with IDA without an obvious cause must be referred for investigation of the upper and lower gastrointestinal tracts in the first instance. To treat IDA, the underlying cause must be corrected and iron stores replenished. The most appropriate method of replacing iron is with oral supplementation

Answer 38

K – Megaloblastic macrocytic anaemia secondary to vitamin B12 deficiency Vitamin B 12 is an essential water-soluble vitamin required for DNA synthesis and red blood cell production. It is absorbed in the terminal ileum only after binding intrinsic factor, which is secreted by gastric parietal cells. The liver is able to store approximately 1 mg of vitamin B12, which is sufficient for 3–4 years; hence vitamin B12 deficiency takes years to manifest. The main causes of vitamin B 12 deficiency are pernicious anaemia, poor dietary intake (vegans) and malabsorption secondary to disease of the terminal ileum. Pernicious anaemia describes the autoimmune loss of parietal cells and/or intrinsic factor, thus preventing the absorption of vitamin B12. It is most common in women over 60 years. Around 90% of patients demonstrate antiparietal antibodies (but some normal women also have these) and 60% are found to have anti-intrinsic factor antibody (which is a more specific marker). Patients with bowel pathology, such as Crohn’s disease (this scenario), have normal levels of intrinsic factor but cannot absorb the vitamin B 12–intrinsic factor complex due to disease of the terminal ileum. Although most patents with pernicious anaemia complain of lethargy and general malaise, specific features of vitamin B 12 deficiency include peripheral neuropathy, smooth tongue, angular stomatitis, depression, dementia and subacute degeneration of the spinal cord. The blood film is likely to show a macrocytic megaloblastic anaemia with hypersegmented neutrophil nuclei (>6 lobes). In addition, serum vitamin B 12 levels are low and ferritin levels are normal, reflecting normal iron stores.

Answer 39

B – β-Thalassaemia major β-Thalassaemia major is an autosomal recessive disorder in which there is a complete lack of production of the haemoglobin β-globin chain. It occurs mainly in Mediterranean and Middle Eastern families and is due to a point mutation on chromosome 11. Because patients with β-thalassaemia major have mutations on both alleles and cannot synthesize any β-globin, they cannot produce functioning adult haemoglobin (HbA: α2β2). This condition typically presents within the first year of life when the production of fetal haemoglobin (HbF: α2γ2) begins to fall. Affected children become generally unwell and fail to thrive secondary to a severe microcytic anaemia. Ferritin levels are normal since there is no iron deficiency. A compensatory increase in the synthesis of HbF and haemoglobin A2 (HbA2: α2δ2) occurs, which can be detected on serum electrophoresis. Clinical features include failure to thrive, lethargy, pallor and jaundice. On examination, there is often hepatosplenomegaly (secondary to extramedullary haematopoiesis), with bossing of the skull and long bone deformity (due to excessive intramedullary haematopoiesis). The treatment of β-thalassaemia major is with regular blood transfusions, aiming to maintain the haemoglobin concentration above 10 g/dL, or with allogeneic bone marrow transplantation. Regular iron chelation therapy (with desferrioxamine) is required to prevent iron overload and deposition in vital organs such as the heart, liver and endocrine glands. If untreated, death is inevitable in the first years of life.

Answer 40

H – Papillary carcinoma The majority (70%) of thyroid tumours are papillary adenocarcinomas; 20% are follicular carcinomas. Both of these tumours occur most commonly in adolescents and young adults, who present with a discrete thyroid nodule. Papillary tumours may be multifocal and they spread to lymph nodes (as in this case). Follicular tumours occur as a single encapsulated lesion, and they spread via blood to the lungs and bone. Treatment is by total thyroidectomy (except for tumours <1 cm, which can be treated by a thyroid lobectomy). Papillary and follicular carcinomas may be thyroid-stimulating hormone (TSH) dependent (i.e. the presence of TSH stimulates their growth). For this reason, after thyroid surgery, patients take lifelong thyroxine, in order to suppress endogenous TSH secretion and reduce the risk of recurrence.

Answer 41

I – Reidel’s thyroiditis Reidel’s thyroiditis is characterized by idiopathic fibrosis of the thyroid gland. Patients present with a slowly growing goitre that is firm and irregular, and for this reason it is difficult to distinguish from cancer without a biopsy. Initially, thyroid function tests are normal, but 30% of affected patients will develop hypothyroidism and hypoparathyroidism. Complications of the fibrosis include tracheal/oesophageal compression and recurrent laryngeal nerve palsy. There is no treatment for Reidel’s thyroiditis, but palliative surgery can be performed if there are compressive symptoms (e.g. dysphagia or stridor).

Answer 42

A – Anaplastic carcinoma This woman has anaplastic carcinoma as indicated by her advanced age and acute presentation. Anaplastic carcinoma accounts for <5% of thyroid tumours but is the most aggressive. It presents in older patients with a hard, symmetrical, rapidly enlarging goitre. Spread is to lymph nodes and local structures, e.g. the trachea (resulting in stridor) and the recurrent laryngeal nerve (leading to hoarseness). There is no effective treatment for anaplastic thyroid tumours, although palliative radiotherapy or debulking surgery can be performed if there is tracheal compression. Most patients (>90%) with anaplastic carcinoma are dead within 1 year.

Answer 43

G – Cushing’s disease Adrenocorticotropic hormone (ACTH; also known as corticotropin) is secreted from the anterior pituitary gland in response to corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH acts on the adrenal cortex to stimulate the release of glucocorticoids and androgens into the circulation. In Cushing’s disease, a pituitary adenoma secretes large amounts of ACTH into the circulation, causing uninhibited glucocorticoid secretion. Patients with glucocorticoid and androgen excess suffer from Cushing’s syndrome, which consists of a vast array of clinical features, including hypertension, central weight gain, a moon face, poor quality skin, bruising, poor wound healing, hirsutism, acne, abdominal striae, oligomenorrhoea, osteoporosis, hyperglycaemia, polyuria, polydipsia, myopathy, depression and psychosis. Cushing’s syndrome can also be caused by iatrogenic steroid prescriptions or the presence of an ectopic ACTH-secreting tumour such as a small cell lung carcinoma. Treatment of Cushing’s syndrome requires correction of the underlying condition (e.g. removal of the pituitary adenoma in Cushing’s disease) and management of any complications such as hypertension. In cases of iatrogenic disease caused by excess steroid therapy, the offending drug should be gradually reduced over a number of weeks and replaced by an alternative ‘steroid-sparing’ drug (e.g. the immunosuppressant azathioprine).

Answer 44

I – Pleural biopsy Mesothelioma is a malignant tumour of the pleura. The effusion of mesothelioma tends to be blood stained, but the definitive diagnosis is made by pleural biopsy

Answer 45

G – Sciatic nerve The sciatic nerve can be damaged with fracture dislocations of the hip or by misplaced gluteal injections. Sciatic nerve palsy results in paralysis of the hamstrings and all the muscles of the leg and foot. Sensation is lost below the knee, except for the medial leg (supplied by the saphenous nerve, a branch of the femoral nerve) and the upper calf (supplied by the posterior femoral cutaneous nerve).

Answer 46

J – Tibial nerve The tibial nerve is particularly vulnerable to damage during posterior dislocations of the knee. It can also be compressed in the posterior tarsal tunnel behind the medial malleolus. A branch of the sciatic nerve, the tibial nerve supplies the flexor compartment of the leg (calf muscles). It also gives rise to the medial and lateral plantar nerves, which supply the intrinsic muscles of the foot as well as plantar sensation. Tibial nerve palsy results in loss of toe flexion, ankle inversion and the ankle jerk. Sensation over the plantar surface of the foot is lost. Affected patients walk with a shuffling gait, as the take-off phase of walking is impaired. There is loss of the lateral longitudinal arch of the foot, and atrophy of the intrinsic foot muscles eventually results in a claw foot.

Answer 47

A – Common peroneal nerve The common peroneal nerve (or common fibular nerve) is a branch of the sciatic nerve that supplies the dorsiflexors and evertor muscles of the foot and sensation to the lateral lower leg and upper foot. The common peroneal nerve lies in close proximity to the fibula, and may become trapped by below-knee plaster casts or damaged with fibular fractures. Features of common peroneal nerve lesions include lack of dorsiflexion (with a resulting foot drop) and loss of sensation in the anterolateral lower leg and dorsum of the foot (except for the lateral aspect of the foot, which is supplied by the sural nerve). The inability to dorsiflex the foot will result in a ‘high-stepping’ gait to ensure that the foot is not scraped along the ground.

Answer 48

9 - This woman is opening her eyes in response to speech (E3), is making noises but no words (V2) and withdraws from painful stimuli (M4): GCS = 3 + 2 + 4 = 9.

Answer 49

E – Ceruloplasmin level Wilson’s disease is an autosomal recessive disease of copper metabolism. In health, copper is transported in the serum bound to ceruloplasmin (ferroxidase) and is excreted in the bile. In Wilson’s disease, there is a defect in copper metabolism such that it is not excreted in the bile and instead accumulates in the tissues. This process suppresses the synthesis of ceruloplasmin, which allows unbound (free) copper to enter the circulation. The high levels of free serum copper accumulate in vital organs such as the liver (resulting in cirrhosis), eye (causing Keiser–Fleischer rings), kidney and basal ganglia of the brain (leading to personality changes). If left untreated, the patient is at risk of developing cirrhosis, renal tubular disease, neurological disease and neuropsychiatric complications. Patients with Wilson’s disease have elevated serum free copper, urinary copper and hepatic copper (via biopsy). Paradoxically, total serum copper is usually low.

Answer 50

C – Antimitochondrial antibody Primary biliary cirrhosis is thought to be an autoimmune disease in which chronic granulomatous inflammation of the interlobular bile ducts causes cirrhosis, portal hypertension and liver failure. It tends to affect middle-aged women, who usually present with pruritis and deranged liver function tests. Xanthelasmas are a recognized feature (as in this case). Up to 98% of patients with primary biliary cirrhosis are positive for the highly specific antimitochondrial antibody M2 subtype. Other investigations used to diagnose primary biliary cirrhosis include hepatic ultrasound imaging, endoscopic retrograde cholangiopancreatography (ERCP) and liver biopsy. The treatment of primary biliary cirrhosis is largely symptomatic. Cholestyramine is used to treat pruritis, and ursodeoxycholic acid may improve ascites and jaundice but is unlikely to prolong life. Without liver transplantation, most patients will die approximately 2 years after the development of jaundice.

Answer 51

I – Hepatitis A IgM Hepatitis A is caused by an RNA virus that is transmitted by the faecal–oral route. It often presents with a non-specific lethargic illness that is followed by the development of jaundice. The earliest serological marker of acute infection is hepatitis A immunoglobulin M (IgM) antibody. Hepatitis A IgG antibodies develop later in the course of the disease, and remain for many years. Hepatitis IgG antibodies usually convey immunity to the disease.

Answer 52

K – Hepatitis C antibody Hepatitis C is caused by an RNA virus that is transmitted through sexual activities and blood products, including the sharing of needles among intravenous drug users. The acute infection is often silent, with many individuals being completely asymptomatic. Hepatitis C antibodies can be used to diagnose previous infection, but take up to 3 months to develop. Approximately 85% of patients with acute hepatitis C infection go on to become chronic carriers, which carries a significant risk of developing cirrhosis, liver failure and hepatocellular carcinoma.

Answer 53

B – Alfacalcidol This patient is hypocalcaemic. Hypocalcaemia in chronic renal failure is due to reduced synthesis of vitamin D. In health, cholecalciferol is formed within the skin in response to sunlight. Cholecalciferol is hydroxylated in the liver to form 25-hydroxycholecalciferol, which is then hydroxylated again in the kidney by 1α-hydroxylase to form 1,25-dihydroxycholecalciferol. This is the active form of vitamin D, which increases the absorption of calcium from the gastrointestinal tract, increases the reabsorption of calcium and phosphate from the kidneys, and reduces parathyroid hormone secretion. The hypocalcaemia of renal failure is treated by supplementing the active form of vitamin D with calcitriol (1,25- dihydroxycholecalciferol) and alfacalcidol (1-hydroxycholecalciferol).

Answer 54

I – Oral calcium channel blocker and fluid restriction Hypertension is an important and common complication of chronic renal failure. Hypertension is largely due to fluid retention, although increased renin secretion may play a role, especially when renal vascular disease is present. Fluid restriction may be enough to reduce the patient’s blood pressure. Oral antihypertensive agents such as calcium channel blockers or β-blockers may also be prescribed. Caution should be taken in prescribing ACE inhibitors, as they can worsen renal failure and promote hyperkalaemia. In patients receiving dialysis, the regimen can be altered to remove fluid as well as waste products in a process known as ultrafiltration.

Answer 55

H – Short Synacthen test This woman presents with postural hypotension. She has vitiligo and some areas of increased skin pigmentation, making her likely to have Addison’s disease. The best investigation to perform is the short Synacthen test. Addison’s disease is primary autoimmune-mediated adrenocortical failure. The action of the adrenal cortex can be described in simplified terms as the secretion of three things: glucocorticoids, mineralocorticoids and adrenal androgens. These usually feed back to the anterior pituitary to reduce ACTH (adrenocorticotropic hormone, also known as corticotropin) secretion. Therefore, failure of the adrenal cortex has many consequences: reduced glucocorticoids (leading to hypoglycaemia and weight loss), reduced mineralocorticoids (leading to hyperkalaemia, hyponatraemia and hypotension), reduced adrenal androgens (leading to decreased body hair and libido) and ACTH excess (leading to increased pigmentation in sun-exposed areas, pressure areas, palmar creases, buccal mucosa and recent scars). The diagnosis of Addison’s disease is by the short Synacthen test. In this investigation, plasma cortisol levels are measured before and half an hour after administration of a single intramuscular dose of ACTH. Normally, the ACTH will result in a rise in cortisol. If there is no rise in cortisol on the second reading, adrenal insufficiency is indicated. Management of Addison’s disease is with the replacement of glucocorticoids and mineralocorticoids (with hydrocortisone and fludrocortisone).

Answer 56

A - 17-Hydroxyprogesterone levels The presentation of clitoromegaly, precocious puberty and accelerated growth in this young girl is indicative of congenital adrenal hyperplasia (CAH). This is an autosomal recessive deficiency of the enzyme 21-hydroxylase. This enzyme is required to synthesize mineralocorticoids and glucocorticoids (but not adrenal androgens) from the hormone precursor 17-hydroxyprogesterone. Because there is a lack of mineralocorticoids and glucocorticoids, there is no negative feedback on the anterior pituitary, resulting in increased ACTH secretion. The high ACTH then causes an increased secretion of adrenal androgens, since this does not require the deficient hormone. The androgens result in the physical features of CAH, namely ambiguous genitalia (in girls), precocious puberty (in girls), accelerated growth in childhood and virilization. The diagnosis of CAH is suggested by finding a raised concentration of the precursor 17- hydroxyprogesterone. Treatment is with hydrocortisone and fludrocortisone to replace the deficient steroids

Answer 57

C - 24-hour urinary 5-hydroxyindole acetic acid The features of paroxysmal flushing, diarrhoea, bronchospasm and abdominal pain precipitated by stress, alcohol and caffeine strongly suggest carcinoid syndrome. Carcinoid tumours are tumours of enterochromaffin cells of the gastrointestinal tract (most commonly of the appendix, ileum or rectum) that secrete serotonin (5-hydroxytryptamine, 5-HT). The secreted 5-HT is carried from the bowel, via the portal vein, to the liver, where it is harmlessly broken down. However, when carcinoid tumours metastasize to the liver, they can secrete 5-HT directly into the bloodstream, bypassing liver metabolism and resulting in the symptoms described above. The presence of carcinoid metastases in the liver that result in symptoms is known as carcinoid syndrome. The diagnosis of carcinoid syndrome is by measuring 24-hour urinary 5-hydroxyindole acetic acid (5-HIAA), a breakdown product of 5-HT. Management is by resection or, in widespread disease, symptomatic treatment with octreotide (a somatostatin analogue that inhibits 5-HT release). Carcinoid tumours are slow growing so, even if disseminated disease is present, patients can live for many years.

Answer 58

L – Wernicke’s encephalopathy Wernicke’s encephalopathy is a reversible condition caused by a severe deficiency of thiamine (vitamin B1). It is often associated with alcohol abuse, the processes involved being a lack of adequate oral intake, hyperemesis and malabsorption caused by gastrointestinal lesions. The triad of features in Wernicke’s syndrome is confusion, ataxia and nystagmus. Ophthalmoplegia is also an important feature. If untreated, Wernicke’s encephalopathy can lead to the irreversible Korsakoff’s syndrome, characterized by confusion, anterograde and retrograde amnesia, and confabulation.

Answer 59

N – Summation gallop rhythm A gallop rhythm is heard when the first (S1) and second (S2) heart sounds are followed by a pathological third (S3) and/or fourth (S4) heart sound. It is most commonly associated with left ventricular failure. When this rhythm is associated with tachycardia, the heart sounds cannot be individually distinguished and therefore ‘summate’ into a single sound. The third heart sound occurs in early diastole, and is caused by the rush of blood entering the ventricle as it relaxes. The presence of a third heart sound can be a normal finding in those below 40 years of age, but when pathological is associated with cardiac failure, mitral regurgitation and dilated cardiomyopathy. On auscultation, the presence of a third heart sound is thought to resemble the phonetic pronunciation of the word ‘Kentucky’. The fourth heart sound occurs just before the first heart sound in the cardiac cycle. It is caused by the atria contracting against abnormally stiff ventricles, and is always pathological. A fourth heart sound can be heard in left ventricular hypertrophy, e.g. caused by aortic stenosis, systemic hypertension, amyloidosis and hypertrophic obstructive cardiomyopathy. On auscultation, the presence of a fourth heart sound is thought to resemble the phonetic pronunciation of the word ‘Tennessee’.

Answer 60

C – Ejection systolic murmur heard at the right second intercostal space only Aortic sclerosis is caused by age-related degeneration of the aortic valve. The condition is asymptomatic and is usually picked up incidentally. On auscultation, there is an ejection systolic murmur heard only in the aortic area, with no associated radiation or ejection click. Aortic stenosis, on the other hand, is usually symptomatic, causing a classic triad of exertional dyspnoea, exertional angina and exertional syncope. Sudden death may also be precipitated. The symptoms of aortic stenosis are due to left ventricular outflow obstruction and myocardial ischaemia secondary to left ventricular hypertrophy. It is a pathological condition caused by rheumatic fever, senile calcification of the valve or a congenital bicuspid aortic valve. On auscultation, there is an ejection systolic murmur that is best heard with the diaphragm in the aortic area (second right intercostal space) and that radiates into the carotid arteries. This may or may not be associated with an ejection click. Other signs of aortic stenosis include a non-displaced left ventricular heave and a slow-rising carotid pulse.

Answer 61

A – Austin Flint murmur Causes of aortic regurgitation include aortic dilatation (in Marfan’s syndrome), infective endocarditis and rheumatic fever. The Austin Flint murmur is heard in patients with significant aortic regurgitation. It is a mid-diastolic low-pitched rumbling murmur best heard at the apex. The murmur is caused when a regurgitated jet of blood passes through the damaged aortic valve and strikes the anterior leaflet of the mitral valve. The more common murmur of aortic regurgitation is a high-pitched early diastolic murmur best heard along the left sternal border with the patient leaning forward at the end of expiration (which is not an option in the present case). Other signs of aortic regurgitation include a collapsing pulse, capillary pulsation in the nail beds (Quincke’s sign), ‘pistol shot’ femoral bruits (Traube’s sign) and visible carotid pulsation (Corrigan’s sign).

Answer 62

I – Reassurance This boy has Peutz–Jeghers syndrome, a condition characterized by multiple bluish-black freckles around the lips, nose, oral mucosa and fingers, as well as multiple gastrointestinal hamartomatous polyps. These polyps are benign and have only a very low malignant potential. The polyps may predispose to gastrointestinal bleeding or intussusceptions, but, in the asymptomatic patient, reassurance is sufficient.

Answer 63

F – Polymyositis Polymyositis is a rare inflammatory disorder of skeletal muscle. Patients present with proximal muscle weakness (hips and shoulder), which may manifest as difficulty in climbing stairs or in standing up from a sitting position. This may be accompanied by swelling, tenderness and wasting of the affected muscle. Blood tests reveal a raised creatine kinase (CK), but the definitive investigation is muscle biopsy, which demonstrates inflammation and necrosis. Polymyositis is associated with underlying malignancy. Anti-Jo-1 antibodies may be present. Treatment is with steroids and immunosuppressants.

Answer 64

A – Antiphospholipid syndrome Antiphospholipid syndrome is characterized by recurrent arterial and venous thromboses (pulmonary embolism, deep vein thrombosis, stroke and peripheral thrombosis), recurrent miscarriage and thrombocytopenia. The diagnosis is confirmed by the presence of specific autoantibodies (anticardiolipin and lupus anticoagulase). Note that the presence of the anticardiolipin antibody will lead to a false-positive VDRL (Venereal Disease Reference Laboratory – syphilis) test. The management of antiphospholipid syndrome involves avoidance of thrombotic risk factors, including smoking and the contraceptive pill, and treating hypertension, hyperlipidaemia and diabetes. Patients who have no history of thrombosis should take low-dose aspirin. After the first thrombotic episode, lifelong warfarin is taken, aiming for an INR of 2.5. If a patient is planning on getting pregnant, warfarin should be stopped (as it is teratogenic) and subcutaneous heparin used instead.

Answer 65

D – Limited cutaneous systemic sclerosis Systemic sclerosis is a connective tissue disorder characterized by thickening and fibrosis of the skin (scleroderma) with involvement of internal organs. There are two forms: a limited cutaneous type (60%) and a diffuse cutaneous type (40%). Limited cutaneous scleroderma is limited to the distal limbs (i.e. distal to the elbows and knees). Other features include a beaked nose and small, furrowed mouth (microstoma). Limited cutaneous scleroderma also encompasses the CREST syndrome, which is characterized by CALCINOSIS, RAYNAUD'S phenomenon, oESOPHAGEAL dysmotility, SCLERODACTYLY and TELANGIECTASIA. Calcinosis is the formation of calcium deposits in the soft tissues, often seen on the pulps of the fingers. Oesophageal dysmotility is manifested as dysphagia and reflux. Sclerodactyly describes the presence of tight, shiny skin over the fingers, producing a fixed flexion deformity. In limited cutaneous scleroderma, the anticentromere antibody is characteristically positive. Pulmonary hypertension is a common internal manifestation. Diffuse cutaneous scleroderma can involve the whole skin of the body. Patients are characteristically positive for the anti-SCL-70 antibody (also known as antitopoisomerase II). In this form of the disease, patients are particularly at risk of a ‘renal crisis’ – a life-threatening malignant hypertension with rapid renal impairment. In contrast, pulmonary hypertension is less common

Answer 66

G – Sjögren’s syndrome The main features of Sjogren’s syndrome are dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostoma). Other features are corneal ulcers, oral candida, vaginal dryness, dyspareunia and respiratory hoarseness. Diagnosis is with Schirmer’s test: a 35 mm-long piece of filter paper is placed under the lower eyelid for 5 minutes – if less than 10 mm becomes moist, it indicates Sjögren’s syndrome. Anti-Ro and Anti-La antibodies may be present. Treatment is with artificial tears and artificial saliva.

Answer 67

H – Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is most common in middle-aged women, and is characterized by arthralgia (joint pain) and rashes. Flare-ups of disease may be triggered by sunlight, the contraceptive pill, infection and stress. Common features are non-erosive arthritis (Jaccoud’s arthritis), a discoid rash on the body, a rash over the cheeks and nose (butterfly rash), fever, depression and myalgia. Treatment of SLE is with analgesia, steroids and immunosuppressants. Lupus can be induced by certain drugs, e.g. isoniazid and penicillamine. Drug-induced lupus is associated with antihistone antibodies. Discoid lupus is a benign variant in which there is skin involvement only.

Answer 68

G – Myelofibrosis Myelofibrosis is a myeloproliferative disease characterized by the replacement of erythropoietic bone marrow with inert fibrotic material. The disease originates from a single abnormal pluripotent stem cell that populates the marrow with abnormal megakaryocytes, which in turn secrete factors known to stimulate fibrosis. Intramedullary fibrosis causes marrow failure and subsequent pancytopenia. In response to anaemia, extramedullary erythropoiesis in the liver and spleen produces the common finding of massive hepatosplenomegaly. Diagnosis is usually based on the combination of a pancytopenic blood film with characteristic tear-drop poikilocytes, a dry bone marrow aspirate and a trephine biopsy showing dense fibrosis of the bone marrow. Myelofibrosis is treated symptomatically with blood transfusion, chemotherapy and splenectomy in severe cases. The average survival time is less than 5 years, although some patients survive for many years. Death usually occurs due to the development of AML, infection or liver failure.

Answer 69

L – Urgent ultrasound scan and compression This man has developed a false aneurysm, which, by definition, involves only one or two layers of the vessel wall. A false femoral artery aneurysm is a recognized complication of angiography, as this artery is often used to gain access to the vasculature. People who use illict drugs may cause a false femoral aneurysm by inadvertently piercing the artery instead of the vein. Initial management is by compression. Ultrasound confirms the diagnosis. Some cases of false aneurysm will require surgical correction because of the risk of rupture, thrombosis and infection.

Answer 70

G – Wernicke’s aphasia Language processing is done predominantly in the left hemisphere. Wernicke’s area (in the left temporal lobe near the primary auditory cortex) is responsible for recognizing and analysing spoken language. Broca’s area (in the left frontal lobe near the primary motor cortex) is responsible for producing coherent speech. Wernicke’s and Broca’s areas are connected by the arcuate fasciculus. In fluent aphasia, the normal number of words is produced, but the wrong words are spoken. In non-fluent aphasia, verbal output is reduced. Damage to Wernicke’s area (Wernicke’s aphasia) results in a fluent aphasia with poor comprehension and poor repetition. This is because the patient cannot analyse what has been said, but is still able to say something thanks to an intact Broca’s area. Conversely, in Broca’s aphasia, there is a non-fluent aphasia with good comprehension and poor repetition. In other words, the patient can wholly understand what is said, but, because they have problems with the motor side of speech, they are unable to repeat what you have said or indeed to say much at all. A lesion in the arcuate fasciculus (which joins the two areas) results in a fluent aphasia with good comprehension but poor repetition – i.e. an intact Wernicke’s area means that the patient can understand what is said, an intact Broca’s area means that they can speak, but the lack of a connection between the two means that they would not be able to repeat a phrase that is told to them.

Answer 71

F – Pseudobulbar palsy The lower cranial nerves (IX to XII) supply the muscles involved in speech and swallowing. Damage to these nerves results in dysphagia and dysarthria. The lesions can either involve the lower motor neurons (leading to bulbar palsy) or the upper motor neurons (leading to pseudobulbar palsy). Pseudobulbar palsy results in a small, contracted tongue and a brisk jaw jerk. Causes include motor neuron disease, multiple sclerosis, brain-stem tumour and brain-stem stroke. Bulbar palsy results in a wasted, fasciculating tongue and a palate that moves very little. Causes include motor neuron disease, syringobulbia, Guillain–Barré syndrome and myasthenia gravis.

Answer 72

A – Broca’s aphasia Language processing is done predominantly in the left hemisphere. Wernicke’s area (in the left temporal lobe near the primary auditory cortex) is responsible for recognizing and analysing spoken language. Broca’s area (in the left frontal lobe near the primary motor cortex) is responsible for producing coherent speech. Wernicke’s and Broca’s areas are connected by the arcuate fasciculus. In fluent aphasia, the normal number of words is produced, but the wrong words are spoken. In non-fluent aphasia, verbal output is reduced. Damage to Wernicke’s area (Wernicke’s aphasia) results in a fluent aphasia with poor comprehension and poor repetition. This is because the patient cannot analyse what has been said, but is still able to say something thanks to an intact Broca’s area. Conversely, in Broca’s aphasia, there is a non-fluent aphasia with good comprehension and poor repetition. In other words, the patient can wholly understand what is said, but, because they have problems with the motor side of speech, they are unable to repeat what you have said or indeed to say much at all. A lesion in the arcuate fasciculus (which joins the two areas) results in a fluent aphasia with good comprehension but poor repetition – i.e. an intact Wernicke’s area means that the patient can understand what is said, an intact Broca’s area means that they can speak, but the lack of a connection between the two means that they would not be able to repeat a phrase that is told to them.

Answer 73

C – Hiatus hernia A hiatus hernia occurs when the stomach herniates through the diaphragm into the thorax. Some patients remain completely asymptomatic, whereas others suffer from intolerable gastro-oesophageal reflux disease and dyspepsia. Complications include weight loss, oesophagitis, oesophageal ulceration, oesophageal stricture and aspiration pneumonia. Diagnosis is usually made during endoscopy or with barium-swallow studies, although many cases are identified incidentally on chest X-ray as a shadow behind the heart with or without an air–fluid level (caused by the presence of gastric contents). Treatment is usually conservative, and involves lifestyle adaptations such as weight loss, smoking cessation and a healthy balanced diet. Proton pump inhibitors may be used to improve symptoms. Surgical repair of medically resistant reflux is with Nissen’s fundoplication, where the fundus of the stomach is wrapped around the lower oesophagus.

Answer 74

I – Toxic megacolon Toxic megacolon refers to life-threatening dilatation of the colon secondary to infective or inflammatory colitis. Patients are usually known to have colitis, and present acutely with abdominal pain, abdominal distension, diarrhoea, bloodstained stools, fever and tachycardia. Abdominal X-ray shows colonic dilatation of >6 cm with or without colonic wall thickening, multiple air–fluid levels and disruption of the haustral pattern. Investigation will usually reveal significantly raised inflammatory markers and electrolyte imbalance. Patients with proven toxic megacolon should be managed in a high-dependency environment and receive fluid resuscitation, corticosteroids, antibiotics and daily abdominal Xrays to assess disease progression. If the dilatation is becoming worse or the patient is clinically deteriorating, a colectomy should be considered.

Answer 75

D – CA 125 The most likely diagnosis in this case is ovarian carcinoma, for which CA 125 is a tumour marker. The clinical features of ovarian malignancy include weight loss, abdominal pain, increasing abdominal girth and ascites. Unfortunately, the symptoms of ovarian malignancy usually occur late, with the result that the disease is often advanced and metastatic at presentation. Diagnosis usually involves transvaginal ultrasonography, CT, ovarian biopsy and measurement of CA 125. Both chemotherapy and surgery are used in the management of ovarian cancer, and have both curative and palliative roles. Radiotherapy is now limited to the palliation of symptoms. Because ovarian malignancy usually presents late, the prognosis is poor. However, if the disease is diagnosed early and treated appropriately, 5-year survival rates for early stage disease can be as high as 95%.

Answer 76

H – Primary sclerosing cholangitis PSC is a condition in which chronic inflammation of the biliary tract results in the development of multiple strictures within the intraand extrahepatic ducts. This condition is associated with inflammatory bowel disease, which is implicated in up to 75% of cases. It is usually seen in young men, and presents with lethargy and pruritis. As the disease progresses, the patient is at risk of developing the symptoms and complications of chronic liver disease, such as jaundice, cholangitis, hepatomegaly, coagulopathy, portal hypertension, oesophageal varices, ascites, encephalopathy and liver failure. There is also a 10% risk of developing cholangiocarcinoma. Diagnosis is based on the presence of deranged liver function tests, hypergammaglobulinaemia and biliary tract imaging – endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP). Treatment is with steroids, ursodeoxycholic acid, cholestyramine and the supplementation of fatsoluble vitamins (A, D, E and K). If there is evidence of liver failure, oesophageal varices or ascites, the patient should be considered for liver transplantation. Without a transplant, death usually occurs within 12 years

Answer 77

G – Left bundle-branch block The ECG findings in this scenario are classic for left bundle-branch block (LBBB). LBBB is always pathological, and is seen in ischaemic heart disease, myocardial infarction, hypertension and cardiomyopathy. In this scenario, it is likely to be a new finding secondary to acute myocardial infarction, in which case it is an indication for thrombolysis. Since the conduction down the left bundle branch is delayed, the QRS complex is prolonged (>0.12 s) and the myocardium depolarizes from right to left, producing dominant R-waves in V6. The subsequent delayed depolarization of the left ventricle produces deep Swaves in V1 and a further R-wave in V6, which completes the ‘M’ pattern in V6. It should be noted that LBBB makes interpretation of the remaining ECG impossible.

Answer 78

I – Right bundle-branch block The ECG of right bundle-branch block (RBBB) shows a prolonged QRS complex (>0.12 s), an RSR pattern in V1 and prominent S-waves in V6. RBBB can be a normal variant in tall, thin adults (as in this case). More sinister causes of RBBB include pulmonary embolus, cor pulmonale and atrial septal defect. Both RBBB and LBBB have an RSR 1 pattern on one side (seen as an ‘M’), with a ‘W’ pattern on the other. Remember ‘MarroW’ (RBBB has an ‘M’ in V1 and a ‘W’ in V6) and ‘WilliaM’ (LBBB has a ‘W’ in V1 and an ‘M’ in V6).

Answer 79

D – Dermatitis herpetiformis Dermatitis herpetiformis is a blistering, intensely itchy rash that develops on the extensor surfaces. It is associated with coeliac disease and is treated with dapsone. There are many cutaneous features of gastrointestinal disease, including the following: * malabsorption: ichthyosis (dry, scaly skin), eczema, oedema * liver disease: jaundice, spider naevi, palmar erythema, leukonychia * renal failure: itching, half white and half red nails * Crohn’s disease: perianal abscess, fistulae, skin tags, aphthous ulcers * ulcerative colitis: erythema nodosum, pyoderma gangrenosum * sarcoidosis: erythema nodosum, lupus pernio (purple indurated lesions).

Answer 80

H – Keratoderma blenorrhagicum This man has Reiter’s syndrome, characterized by arthritis, urethritis and iritis. There are two skin features that can develop alongside this disease: keratoderma blenorrhagicum and circinate balanitis. Keratoderma blenorrhagicum describes the presence of pustular, crusty, yellow–brown papular lesions on the soles of the feet that are clinically and histologically indistinguishable from pustular psoriasis. It is seen in 15% of men with Reiter’s syndrome. Circinate balanitis describes an annular, erythematous reaction on the glans penis, and occurs in 30% of men with Reiter’s syndrome.

Answer 81

B – Autosomal recessive polycystic kidney disease Autosomal RECESSIVE polycystic kidney disease (ARPKD) is a genetic condition caused by mutations in the PKD1 or PKD2 genes that result in the formation of multiple fluid-filled cysts within the collecting ducts of the kidney and the liver. Severe ARPKD can present during labour with respiratory difficulties and acute renal failure. More insidious presentations are common, and typically combine failure to thrive, hypertension and worsening renal function. Patients who present earlier tend to have more renal disease in proportion to hepatic disease, whereas the opposite is true of those who present later on in life. The majority of patients with ARPKD eventually require renal replacement therapy. This condition should not be confused with autosomal DOMINANT polycystic kidney disease, which presents later in life and is associated with berry aneurysms and subarachnoid haemorrhage.

Answer 82

M – Unilateral renal agenesis Unilateral renal agenesis is a relatively common condition in which one kidney does not develop. The remaining kidney hypertrophies and compensates for the missing kidney. Patients are often completely asymptomatic and are diagnosed incidentally during the investigation of other disease or post mortem. Sometimes the condition is discovered during the investigation of hypertension or an abdominal mass.

Answer 83

C – Acute aortic regurgitation This is a case of acute aortic regurgitation secondary to a type A (i.e. involving the ascending aorta) dissecting aortic aneurysm. Since this is an acute event, the left ventricle has had no time to compensate for the increased demands placed upon it, resulting in left ventricular failure and cardiogenic shock. On auscultation of aortic regurgitation, there is usually an early diastolic murmur at the left sternal border, which is best heard with the patient sitting forward at the end of expiration. Patients are said to have a water-hammer (collapsing) pulse and a wide blood pressure index (i.e. a high systolic and a low diastolic blood pressure). In chronic aortic regurgitation, seen in conditions such as Marfan’s syndrome and congenital bicuspid aortic valve, the apex is often displaced laterally due to left ventricular dilatation. Aortic regurgitation is associated with a number of eponymous signs that are often referred to in examinations: * Corrigan’s sign: visible pulsation of the carotid arteries * de Musset’s sign: head bobbing * Quincke’s sign: pulsation of the nail beds * Traube’s phenomenon: pistol shot sound on femoral artery auscultation.

Answer 84

A – Acute lymphoblastic leukaemia Acute lymphoblastic leukaemia (ALL) is the most common leukaemia in children, and is caused by the clonal proliferation of lymphoid precursor (blast) cells that have been arrested at an early stage of development. The blast cells infiltrate the marrow and lymphoid tissue, causing pancytopenia and lymphadenopathy, respectively. The central nervous system (CNS) can also be affected, causing headache, vomiting, meningism, cranial nerve palsies and seizure. The marrow failure and subsequent pancytopenia produce the common features of anaemia, bleeding/bruising and infection. Bone pain is another common presenting symptom. A full blood count confirms anaemia and thrombocytopenia, but demonstrates a high white cell count (due to circulating blast cells). The investigation of choice is bone marrow aspiration, which shows a hypercellular marrow with >20% blasts. Treatment involves the use of chemotherapy, as well as supportive measures such as transfusion and antibiotics. Chemotherapy is traditionally delivered in three main stages: remission induction, consolidation and maintenance (which can be for a number of years). Since patients with ALL are at high risk of neurological disease, they are often given CNS prophylaxis in the form of intrathecal methotrexate and radiotherapy. The prognosis of ALL is good with appropriate treatment.

Answer 85

B – Acute myeloid leukaemia Acute myeloid leukaemia (AML) is caused by the proliferation of myeloid precursor cells. This condition is generally seen in adulthood and is rapidly fatal if untreated. AML is seen as a new disease and in patients with myeloproliferative disorders. Patients with Down’s syndrome are at increased risk of both ALL and AML, with the risk of AML being highest in the first 3 years of life. AML is increasingly seen in patients who have received chemotherapy in the past for other malignancies such as lymphoma. The presentation of AML is variable. Many sufferers are asymptomatic and are diagnosed incidentally whereas others become very unwell very quickly. Marrow failure caused by blast infiltration causes anaemia, thrombocytopenia and neutropenia. Investigation usually shows a significantly raised white blood cell count, although it may be normal or even low. Cellular inclusions called Auer rods which are seen on microscopy are pathognomonic of AML. Management of AML involves blood and platelet transfusion, treatment of infections and chemotherapy. In patients less than 55 years of age, stem cell transplantation is considered. The prognosis of AML is worse than that of ALL. Up to 80% of patients can be expected to achieve remission, but most relapse, and the cure rate is only 30%. The prognosis is worse in elderly people and in patients with a history of myeloproliferative disorders.

Answer 86

E – Chronic myeloid leukaemia Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. There is excessive proliferation of myeloid cells in the bone marrow. Patients typically have massive splenomegaly, anaemia, bruising and infection on a background generalized illness. Up to 90% of CML patients have a genetic translocation involving chromosomes 9 and 22 known as the Philadelphia chromosome. A blood film shows myeloblasts (granulocyte precursors) and granulocytosis. Patients with CML but without the Philadelphia chromosome have a worse prognosis than those with the translocation. There are three stages of disease in CML: the chronic phase (responsive to treatment), the accelerated phase (where disease is difficult to control) and the blast crisis phase (where disease progresses into an acute leukaemia, usually AML). The median survival is 5 years. Death usually occurs within months of blast transformation (from bleeding and infection). Chemotherapy is often used, but allogeneic stem cell transplantation is the only hope of cure. Chronic lymphocytic leukaemia (CLL) accounts for 30% of leukaemias in the over- 50s. It is characterized by the accumulation of incompetent CD5+ B cells that fail to secrete antibody (instead secreting light chains). Patients present with anaemia, painless lymphadenopathy, splenomegaly and infection. A blood film reveals a mature lymphocytosis (with anaemia and thrombocytopenia). The median survival is 6 years. CLL can occasionally transform into a high-grade aggressive lymphoma (Richter’s transformation).

Answer 87

I – Space-occupying lesions A constant, dull headache that is worse in the morning (after periods of being supine) and exacerbated by coughing, straining and laughing is typical of an underlying space-occupying lesion. The headache may be accompanied by nausea and vomiting, blurring of vision and focal neurological signs. Fundoscopy may show bilateral papilloedema. This history requires an urgent CT head scan to confirm the presence of a lesion.

Answer 88

C – Giant cell arteritis Giant cell arteritis is an inflammatory vasculitis of the cranial branches of the arteries arising from the aorta. It is most common in the over-50s and twice as frequent in women. Patients present with malaise, fever, temporal headache, scalp tenderness and pain on chewing (jaw claudication). On examination, the temporal artery is tender, enlarged and non-pulsatile. Some cases are associated with polymyalgia rheumatica (proximal muscle pain and stiffness without weakness). Diagnosis is with temporal artery biopsy, which shows patchy granulomatous necrosis with giant cells. Not all of the artery may be affected, so a negative biopsy result does not rule out disease. Furthermore, arteritis of the ophthalmic artery can lead to ischaemic optic neuritis and permanent blindness, so it is important to treat this condition immediately if there is clinical suspicion before performing biopsy. Treatment is with oral prednisolone.

Answer 89

G – Sagittal sinus thrombosis Cerebral venous sinus thrombosis describes a clot in one of the dural venous sinuses of the brain. The clinical features can depend on the underlying location of the thrombosis. Presentation is generally with a sudden-onset headache, seizures and signs of raised intracranial pressure, e.g. papilloedema, hypertension and bradycardia. More specific symptoms may be seen with cavernous sinus thrombosis (proptosis, ptosis, ophthalmoplegia, reduced sensation in the first division of the trigeminal nerve) and transverse sinus thrombosis (hemiparesis). Risk factors for the development of venous thromboses include contraceptive pill use, pregnancy, nephrotic syndrome and thrombophilias (protein S or C deficiency and antithrombin III deficiency). The diagnosis is confirmed by demonstrating the clot on CT or MRI. In sagittal sinus thrombosis, the ‘empty delta sign’ may be seen (a triangular area of enhancement within the sagittal sinus with a relatively low-attenuating centre). Management is with anticoagulation.

Answer 90

F – Syringomyelia Syringomyelia describes the presence of a longitudinal fluid cavity (syrinx) within the spinal cord. These cavities are usually in the cervical segments, and disrupt the spinothalamic tracts. Patients present in their 20s or 30s with a segmental dissociated loss of spinothalamic function (i.e. spinothalamic function above and below the lesion is preserved). Dorsal column and motor function remain intact. When a syrinx affects the brain stem, the condition is called syringobulbia. Diagnosis of syringomyelia is by MRI, and management is by surgical decompression of the syrinx. Syringomyelia may be associated with an Arnold–Chiari malformation, congenital herniation of the cerebellar tonsils through the foramen magnum at the base of the skull. Syringomyelia may also be caused by tumours of, or trauma to, the spinal cord.

Answer 91

D – Central cord syndrome Central cord syndrome is the most common spinal cord lesion. It occurs in older people with cervical spondylosis who sustain a hyperextension injury. There is flaccid weakness of the arms, but motor and sensory fibres to the lower limb are comparatively preserved, as these are located more peripherally in the spinal cord. Central cord lesions have a fair prognosis.

Answer 92

E – Posterior cord syndrome Hyperextension injuries can result in loss of dorsal column function (posterior cord syndrome). These injuries are very rare, and motor and sensory function is preserved. Gait is impaired due to impaired proprioception. The prognosis of posterior cord lesions is good. Anterior cord syndrome occurs secondary to a flexion–compression injury. There is loss of neurological function of the anterior two-thirds of the spinal cord, namely the spinothalamic (pain and temperature) and corticospinal (motor) tracts. There is greater motor loss in the legs than in the arms. Anterior cord syndrome has the worst prognosis of all spinal cord lesions.

Answer 93

D – Poliomyelitis Poliomyelitis is caused by the poliovirus. Infection occurs through the nasopharynx and is more common in developing countries. The virus infects the grey matter of the nervous system, especially the anterior horn cells in the lumbar region. Initial infection causes a mild fever and headache, progressing to aseptic meningitis. Weakness then starts in one muscle group and can progress to widespread paresis. Respiratory failure occurs if the intercostal muscles are affected. Diagnosis is confirmed by culturing poliovirus from cerebrospinal fluid (CSF) or stool. Management is with bed rest (as exercise worsens or precipitates paralysis) and ventilation if required. Any muscle weakness that remains after 1 month of initial infection is likely to remain permanent. Prevention of poliomyelitis is with immunization by a live vaccine.

Answer 94

A – Cerebral abscess Bacteria can enter the cerebrum either via the blood or directly (from the paranasal sinuses or the middle ear). Features of cerebral abscesses include fever, headache, meningism and drowsiness. An abscess can also present chronically as a mass lesion (with seizures, focal neurological signs and raised intracranial pressure). A CT scan will demonstrate an abscess as an area of low density surrounded by a capsule. Treatment is with antibiotics, although a burr-hole aspiration may be needed. The mortality rate is 20%

Answer 95

F – Subacute sclerosing panencephalitis Subacute sclerosing panencephalitis is a fatal disorder caused by the measles virus. It begins many years after the original measles infection with insidious intellectual deterioration, apathy, myoclonic jerks, rigidity and dementia. The EEG is distinctive (showing periodic bursts of triphasic waves). There is no effective treatment, and death occurs within years.

Answer 96

I – Squamous cell carcinoma Squamous cell carcinoma (SCC) is a malignant tumour of keratinocytes that occurs in those aged over 50 in sun-damaged sites. Predisposing factors for their development include X-ray exposure, smoking, human papillomavirus and a genetic susceptibility. SCCs typically have raised everted edges with a central scab. Management is by surgical excision, with lymph node dissection or radiotherapy if there is evidence of spread. An actinic keratosis (also known as a solar keratosis) is a hyperkeratotic, yellow– brown crusty lesion that occurs on sun-damaged sites. Although these lesions are benign, they are premalignant to SCC. For this reason, actinic keratoses should be removed, e.g. by excision, shaving or cryotherapy.

Answer 97

J – Superficial spreading malignant melanoma Malignant melanoma is a malignant tumour of melanocytes and is the most lethal of skin tumours. It is most common in white people living near the equator, and is twice as common in women. Risk factors include repeated ultraviolet exposure, previous malignant melanoma, multiple melanocytic naevi and having a large congenital naevus. Primary treatment is by surgical excision. Prognosis is related to tumour depth (Breslow score). Superficial spreading malignant melanoma is the most common type of malignant melanoma. It occurs most often in younger females on the leg. The tumour is macular with an irregular edge, and may itch or bleed.

Answer 98

G – Lentigo maligna melanoma The original lesion that this woman has on her cheek is a lentigo maligna (or Hutchinson’s malignant freckle) – a large irregular pigmented area that occurs most often in elderly people on sun-exposed skin. Lentigo maligna is associated with malignant transformation to melanoma (lentigo maligna melanoma). Thickening, darkening or ulceration within a lentigo maligna signals the onset of malignancy.

Answer 99

G – Idiopathic thrombocytopenic purpura In idiopathic thrombocytopenic purpura (ITP), autoantibodies are formed against platelets, resulting in their premature destruction. This condition, which is usually seen shortly after a viral illness such as varicella-zoster infection, causes the platelet count to fall rapidly. The patient usually develops a purpuric rash and experiences bleeding from the skin and mucous membranes. In very severe cases, there may be more significant bleeding, including intracranial haemorrhage. Investigation shows a normal prothrombin time (PT) and a normal activated partial thromboplastin time (APTT), since the clotting factors and clotting cascade are unaffected. The bleeding time is prolonged, as the thrombocytopenia reduces the rate of platelet activation and aggregation at the site of injury. The disease is usually self-limiting and requires no specific management. In severe disease, corticosteroids or immunoglobulin may be used.

Answer 100

L – Von Willebrand disease In von Willebrand’s disease, there is a quantitative or qualitative deficiency of von Willebrand factor (vWF), which is a protein that promotes platelet adhesion to the vascular wall and subsequent aggregation. It also plays a role in the transport of factor VIII and in preventing its premature destruction. There are three main types of von Willebrand disease. In type 1 disease, there are reduced levels of normal vWF. Type 2 disease is due to the production of defective vWF. In type 3 disease, there is a total lack of vWF production and a significantly reduced level of factor VIII. Types 1 and 2 disease are autosomal dominant conditions. Type 3 disease is autosomal recessive. Types 1 and 2 disease are usually mild, with patients complaining of bruising, epistaxis and menorrhagia. Type 3 disease is more severe, and may cause bleeding into joints and soft tissues (haemarthrosis). Investigation of vWF shows a normal platelet level and a normal PT. APTT may be slightly prolonged due to reduced levels of factor VIII in severe disease. The bleeding time is increased, as platelets fail to adhere to the vessel wall and aggregate.

Answer 101

H – Thiazide diuretics Thiazide diuretics, such as bendroflumethiazide, are known to trigger hyperglycaemia and exacerbate diabetes. The risk is more prominent in patients taking higher doses. Other classes of drug that may induce diabetes include β-blockers, antipsychotics and steroids.

Answer 102

L – Pre-renal acute renal failure secondary to hypovolaemia Acute renal failure can be defined as the deterioration of renal function over hours or days. By far the most common cause of acute renal failure is hypoperfusion of the kidney, referred to as pre-renal acute renal failure. This is usually seen with hypovolaemia secondary to conditions such as acute blood loss, vomiting, diarrhoea and burns. It may also occur in normovolaemic patients with sepsis, cardiac failure or renal artery stenosis. Investigation demonstrates high serum urea, creatinine and potassium concentrations, and a poor urine output. Prerenal acute renal failure is treated by correcting the underlying condition and restoring the patient’s circulating volume with intravenous fluids. If the kidneys are hypoperfused for a significant amount of time, autoregulatory mechanisms within the renal vasculature fail, causing tubular cell damage and death. This condition is known as acute tubular necrosis (ATN) and results in failure of active sodium reabsorption and failure to concentrate the urine. The urine produced in ATN typically has a high sodium concentration, a low osmolarity, a low urine: serum urea ratio and a low urine:plasma osmolarity ratio. ATN usually resolves if the underlying cause is corrected and appropriate fluid therapy is delivered, although recovery may take weeks.

Answer 103

C – Haemolytic uraemic syndrome In haemolytic uraemic syndrome (HUS), there is acute renal failure, microangiopathic haemolytic anaemia and thrombocytopenia. This condition is classically seen in childhood following gastroenteritis caused by Escherichia coli O157, which produces nephrotoxic verotoxins. Other gastrointestinal and respiratory tract pathogens may also cause HUS, but are seen less frequently. The haemolytic anaemia and thrombocytopenia are due to erythrocyte and platelet destruction within fibrin meshes that are deposited on affected endothelial membranes. Other features of HUS include haematuria, proteinuria, purpuric rash and central nervous system complications. Treatment of HUS is supportive. Some patients require temporary peritoneal dialysis or haemodialysis. Occasionally, renal function is permanently compromised, necessitating longterm renal replacement therapy and renal transplantation.

Answer 104

A – Bacillus cereus Bacillus cereus is a spore-producing bacterium that can induce diarrhoea and vomiting within hours of ingestion. Infection is usually due to consuming rewarmed rice that has been contaminated with spores, e.g. rice that has been boiled and left several hours before frying (hence the term ‘Chinese fried rice syndrome’). It is usually a relatively short-lived infection and clears up within 24 hours. Antibiotics are not indicated.

Answer 105

G – Staphylococcus aureus Staphylococcus aureus food poisoning is caused by heat-resistant enterotoxins that interact with the vagus nerve, causing vomiting within hours of ingestion. Diarrhoea is not usually a feature. The illness is self-limiting and requires symptomatic treatment only.

Answer 106

F – Rotavirus Rotavirus infection commonly occurs in children and hospitalized patients during the winter period. It spreads readily from person to person and has an incubation period of 2 days. The patient may have a prodrome of upper respiratory tract illness followed by development of diarrhoea and vomiting. The illness is selflimiting and usually requires no treatment other than supportive measures. Some children and frail adults require intravenous fluids to treat dehydration and electrolyte imbalance that is not responding to oral rehydration.

Answer 107

B – Complex partial seizure A simple partial seizure is one where consciousness is preserved. In complex partial seizures, consciousness is affected. Patients having a complex partial seizure stop what they are doing, stare blankly and may display automatisms (e.g. lip smacking). This may be preceded by complex hallucinations. After a few minutes, consciousness returns and the patient is drowsy.

Answer 108

F – Muscle biopsy This woman has dermatomyositis, a connective tissue disease characterized by proximal muscle weakness (hips and shoulders) with characteristic skin lesions (a purple rash on the eyelids and scaly pink papules on the knuckles). The best investigation is a muscle biopsy, which demonstrates inflammation and necrosis.

Answer 109

H – Schirmer’s test This woman has Sjögren’s syndrome, characterized by dry eyes (keratoconjunctivitis sicca) and a dry mouth (xerostoma). Diagnosis is with Schirmer’s test. A 35 mm-long piece of filter paper is placed under the lower eyelid for 5 minutes – if less than 10 mm becomes moist, this indicates Sjögren’s syndrome.

Answer 110

A – Angiography This woman has Takayasu’s arteritis, a vasculitis of the aorta and the other major arteries. Inflammation causes stenosis of the arteries, which leads to absence of distal pulses and limb claudication. Angiography will demonstrate stenosis of the affected vessels.

Answer 111

E – Joint aspiration and microscopy The likely diagnosis in this man is acute gout. The diagnosis can be confirmed by performing a joint aspiration and sending for microscopy. The presence of negatively birefringent, needle-shaped crystals is indicative of gout. In practice, you would send some joint fluid for culture anyway to rule out septic arthritis.

Answer 112

F – Haemorrhage into a cyst This woman has a history of a thyroid cyst. The acute presentation of neck pain and growth of the lesion suggest haemorrhage into the cyst. Haemorrhage can result in tracheal compression and stridor. If possible, aspiration of the cyst contents should be performed to alleviate tracheal compression and maintain airway patency. If aspiration is not possible, surgical intervention may be required.

Answer 113

G – Mitral valve prolapse Mitral valve prolapse is a relatively common condition that tends to affect young women and those with a history of congenital heart disease such as atrial septal defect and patent ductus arteriosus. Many people with mitral valve prolapse are asymptomatic. Those who experience symptoms tend to complain of atypical chest pain and palpitations that are exacerbated by exercise. Less common complications include postural hypotension, syncope, bacterial endocarditis, cerebral and systemic emboli, and ventricular arrhythmia. On auscultation, there may be a midsystolic click, which is sometimes associated with a late-systolic murmur. Diagnosis is by echocardiography. Treatment is mainly symptomatic with ‘pill in the pocket’ β-blockers that are taken during episodes of pain and palpitations. Due to the increased risk of bacterial endocarditis, patients with mitral valve prolapse should receive antibiotic prophylaxis prior to invasive procedures.

Answer 114

D – Decubitus angina Decubitus angina describes typical angina pain on lying flat at night time. The reabsorption of peripheral fluid into the venous circulation that occurs while lying flat places additional strain on the heart. The diseased coronary arteries are unable to deliver adequate blood to supply the increased myocardial oxygen demand. Decubitus angina occurs when anti-angina therapy is suboptimal and when coronary artery disease is severe.

Answer 115

H – Oesophageal spasm Oesophageal spasm is rare, and is often confused with angina. It classically presents with retrosternal chest pain, with or without dysphagia. It is caused by abnormal peristaltic contraction in the distal half of the oesophagus, which may occur spontaneously or secondary to precipitating factors such as hot food. The pain is very similar to angina and is classically partially relieved by nitrates and calcium channel blockers. Twenty-four-hour oesophageal manometry may show paroxysmal oesophageal contractions. Barium swallow may demonstrate a ‘corkscrew oesophagus’ caused by the abnormal peristalsis, although this is seen only during active spasm. Conservative treatment is with nitrates or calcium channel blockers. In severe disease, botulinum toxin may be injected into the oesophagus to provide temporary relief. Surgical treatment is indicated in disabling disease.

Answer 116

F – Essential tremor Tremors are rhythmic oscillating movements of a limb, part of a limb or the head. Essential tremors are slow, are often familial, and may be made more obvious during certain actions such as writing. Essential tremors are characteristically improved with alcohol. β-Blockers can be used to improve such tremors. Physiological tremors are seen in normal people, and have a frequency of 8– 15Hz. Physiological tremors can be exaggerated with anxiety, fatigue, fever and alcohol withdrawal. The resting tremor is pathognomonic of Parkinson’s disease and has a frequency of 4–6 Hz. It is characteristically pill-rolling and is usually asymmetrical.

Answer 117

K – Rubral tremor Lesions in the superior cerebellar peduncle cause a rubral tremor – a violent, large-amplitude, postural tremor that worsens as the target is approached. It is common in advanced multiple sclerosis and can be disabling.

Answer 118

I – Primary hyperparathyroidism Primary hyperparathyroidism is one of the most common causes of nonmalignant hypercalcaemia. The symptoms of hypercalcaemia include lethargy, polyuria, polydipsia, peptic ulcer disease, stone formation and depression. Patients with very high serum calcium levels are at risk of cardiac arrest. In health, calcium metabolism is largely regulated by parathyroid hormone (PTH), which is secreted from the parathyroid glands. PTH increases serum calcium concentration by promoting bone resorption, renal phosphate excretion and vitamin D synthesis. The net effect of PTH is a rise in serum calcium and a fall in serum phosphate. Primary hyperparathyroidism is usually due to a single parathyroid adenoma that autonomously secretes excessive amounts of PTH. It is diagnosed by identifying hypercalcaemia in the presence of raised PTH levels. Treatment is by parathyroidectomy. Significant hypercalcaemia should be treated with fluid resuscitation and bisphosphonates.

Answer 119

M – Tertiary hyperparathyroidism Tertiary hyperparathyroidism occurs following a prolonged period of secondary hyperparathyroidism. The parathyroid glands hypertrophy and begin to secrete PTH autonomously, i.e. this is no longer a physiological response to negative feedback (as in secondary hyperparathyroidism). The patient will usually have a high serum calcium level and a high PTH level. It is best to avoid the development of tertiary hyperparathyroidism by the correct and early management of secondary hyperparathyroidism. In severe disease, it is possible to remove the majority of the parathyroid tissue to reduce hormone levels.

Answer 120

E – Dilated cardiomyopathy In dilated cardiomyopathy, the left ventricle becomes dilated and inefficient, placing the patient at risk of arrhythmia (particularly atrial fibrillation), embolic disease and heart failure. The condition is occasionally familial, but is usually acquired and often secondary to excess alcohol consumption, ischaemic heart disease, metabolic disease, myocarditis and primary muscular diseases, including muscular dystrophy. Treatment is largely symptomatic, with arrhythmias and heart failure being treated as usual. Patients with dilated cardiomyopathy require anticoagulation to reduce the risk of embolic disease. Those who are known to experience dangerous ventricular arrhythmia require an internal cardiac defibrillator. Cardiac transplantation is a last resort for disease that is refractory to maximum medical therapy.

Answer 121

B – Atrial myxoma Atrial myxoma, despite being relatively rare, is the most common tumour of the heart. It is a benign gelatinous neoplasm and is predominantly found attached to the septal wall of the left atrium by a pedicle. Symptoms include chest pain, dyspnoea, fever, lethargy and weight loss. Auscultation my reveal a loud first heart sound and a diastolic ‘plop’ due to prolapse of the tumour through the mitral valve. The presentation is similar to infective endocarditis and can cause diagnostic difficulties. Atrial myxomas can often embolize (with typical embolic consequences), but they do not metastasize. Echocardiography is the investigation of choice, and usually identifies a cystic polypoid mass. Treatment is by surgical excision. If removal is not complete, myxoma may recur. The Carney complex is an autosomal dominant condition characterized by atrial and cutaneous myxomas, spotty skin hyperpigmentation and endocrine overactivity. It is associated with around 10% of cases of atrial myxoma.

Answer 122

G – Myocarditis Myocarditis is most commonly due to viral infection with Coxsackie B virus. Other causes include autoimmune disease, rheumatic fever, diphtheria, and a multitude of other viral, bacterial and fungal pathogens. Presentation is usually with a period of general illness, lethargy, fever and palpitations, followed by symptoms of left ventricular failure. Definitive diagnosis is often difficult, as evidence of infection is rarely found. Plasma troponin and cardiac enzymes are elevated in proportion to the extent of damage. Endomyocardial biopsy is sometimes employed to aid diagnosis. Treatment is predominantly symptomatic, including management of congestive cardiac failure and arrhythmias. Patients are advised to avoid exertion during the illness, as this may precipitate fatal ventricular arrhythmias. Some people recover fully, while others have a prolonged illness resulting in dilated cardiomyopathy. A number of patients die in the acute stages due to arrhythmias, congestive cardiac failure and refractory cardiogenic shock.

Answer 123

A – Abducens nerve palsy This woman may have a brain tumour. The consequent raised intracranial pressure can result in compression of the abducens nerve on the temporal bone. The abducens nerve innervates the lateral rectus, the muscle that abducts the eye. A palsy of this nerve results in diplopia on gazing laterally towards the side of the lesion, since there is no abduction of the eye on this side. In this scenario, the patient experiences diplopia on left lateral gaze, signifying a left abducens nerve palsy.

Answer 124

G – Temporal lobe lesion The upper fibres from the optic tract travel through the temporal lobe and the lower fibres pass through the parietal lobe. Whereas lesions in the optic tract cause a contralateral homonymous hemianopia (see above), a lesion in the temporal lobe will result in a contralateral homonymous upper quadrantopia (loss of the upper quarter of the visual field on the same side in both eyes). Similarly, parietal lobe lesions cause a contralateral homonymous lower quadrantopia. Occipital lobe lesions result in a homonymous hemianopia, often with macular sparing.

Answer 125

B – Dermatitis herpetiformis Dermatitis herpetiformis is an intensely itchy, blistering rash that is associated with coeliac disease. It is usually found on the extensor surfaces of the elbows and knees, but can also be found on the back, buttocks and forehead. Treatment usually involves the implementation of a gluten-free diet in combination with oral dapsone and topical corticosteroids.

Answer 126

D – Marjolin’s ulcer Marjolin’s ulcer is the development of a squamous cell carcinoma occurring in an area of scarred or traumatized skin, such as a burn injury, chronic wound or venous ulcer. Lesions appear as raised, fleshy, firm papules that grow slowly. Treatment is by wide local excision.

Answer 127

A – Arterial ulcer This man has features of intermittent claudication (cramping in the lower limbs on exertion). This is due to underlying ischaemia (from arterial disease). Other features of ischaemia include cold feet, hair loss, toenail dystrophy, dusky cyanosis and ischaemic ulceration. Arterial ulcers are deep, painful and sharply defined, and usually occur on the shin or foot. The peripheral pulses may be reduced or absent on examination. Contrast angiography will help define arterial lesions, which may be improved by angioplasty or vascular reconstruction. Venous ulcers occur most often in women after middle age. They occur over a background of deep venous insufficiency. There are many stages of skin changes in venous disease, beginning with oedema and a brown discoloration of the skin. The brown colour comes from haemosiderin deposits, which occur secondary to extravasation of red cells from leaky capillaries. The next stages are an eczema-like appearance, with hardening and constriction of the skin around the ankle (lipodermatosclerosis). The tightening of the skin around the ankle that occurs with lipodermatosclerosis, along with the oedema of the leg proximal to this, results in an ‘inverted champagne bottle’ appearance. Ulceration of the affected skin often follows trauma and usually affects the medial gaiter area (the gaiter area stretches from the ankle to the proximal calf, much like the gaiters used in hiking to prevent muddy water from getting into boots).

Answer 128

H – Pyoderma gangrenosum Pyoderma gangrenosum is a skin condition that is associated with inflammatory bowel disease (as in this patient), rheumatoid arthritis and myeloid blood dyscrasias (e.g. acute and chronic myeloid leukaemias). It initially appears as purple papules, which enlarge and break down to become deep, necrotic ulcers with a dark-red border. Pyoderma gangrenosum is most common on the legs, but can develop anywhere.

Answer 129

E – Sick sinus syndrome Sick sinus syndrome is caused by a dysfunctional sinoatrial node, usually secondary to age-related fibrosis. It is often diagnosed using a 24-hour ECG tracing requested for patients experiencing palpitations or symptomatic bradycardia such as dizzy spells and syncope. The tracing usually shows sinus bradycardia, atrioventricular block or asystole interspersed with periods of supraventricular tachycardia, such as junctional tachycardias or atrial fibrillation. There is no specific treatment. Although pacemaker insertion may be indicated in cases with severe symptoms, this does not affect prognosis. Anticoagulation is recommended in patients at risk of thromboembolic disease.

Answer 130

I – Ventricular fibrillation In ventricular fibrillation, the ventricles contract ineffectively at a rate of 300–600 beats/min. The ECG tracing shows a rapid, irregular rhythm with a fibrillating baseline. The speed and haphazard nature of ventricular contraction means that no cardiac output is possible, and vital organs, including the brain, are not perfused, resulting in rapid death. The only treatment is DC cardioversion according to the Advanced Life Support Guidelines. Adjuncts to treatment include basic life support, intravenous adrenaline (epinephrine) and intravenous amiodarone.

Answer 131

G – Torsades de pointes Torsades de pointes, a specific form of ventricular tachycardia, is a broad complex ventricular arrhythmia caused by prolonged ventricular repolarization, which is seen on ECG as an extended QT interval. A prolonged QT interval may be congenital or acquired. Long-QT syndromes, such as Romano–Ward syndrome, are congenital diseases caused by ion channel abnormalities, and are commonly associated with torsades de pointes. Acquired disease is usually secondary to electrolyte imbalance or drug side-effects. Patients with hypomagnesaemia and hypokalaemia are at particular risk of torsades de pointes. Drugs that are known to trigger torsades de pointes include class Ia antiarrhythmic agents (disopyramide and procainamide), tricyclic antidepressants (amitriptyline and imipramine), phenothiazine antipsychotics (chlorpromazine and prochlorperazine) and nonsedating antihistamines (loratidine). Torsades de pointes is seen on ECG as a regular broad complex tachycardia with a varying axis whereby the QRS complexes repeatedly switch from an upright to a horizontal position. The patient often experiences palpitations, dizziness, chest pain and syncope. The rhythm usually aborts spontaneously, but has the potential to degenerate into ventricular fibrillation. Prolonged episodes of torsades de pointes that are associated with haemodynamic instability require urgent DC cardioversion.

Answer 132

D – Hypercalcaemia Hypercalcaemia of malignancy is usually due to the ectopic production of parathyroid hormone-related protein, which mimics the action of parathyroid hormone and mobilizes calcium into the bloodstream. Hypercalcaemia may also be due to lytic bone metastases or the activation of osteoclasts, as seen in breast cancer and myeloma, respectively. Acute hypercalcaemia usually presents with confusion, polyuria, polydipsia, constipation and mood changes, and is ultimately diagnosed by measuring serum calcium. Treatment should begin with intravenous fluid hydration, aiming for 3–6 L of 0.9% saline over 24 hours. In severe cases, the patient should receive an intravenous bisphosphonate (e.g. pamidronate), which reduces bone resorption. Calcitonin may be given in hypercalcaemia refractory to hydration and bisphosphonate therapy.

Answer 133

L – Syndrome of inappropriate ADH secretion SIADH in malignancy is usually due to ectopic ADH secretion from tumour cells. The most common tumour causing this condition is small cell lung carcinoma. The water retention caused by the excessive production of ADH results in a dilutional hyponatraemia, which, when severe, can cause seizures and permanent neurological damage. In addition to a low serum sodium concentration, the patient will also have raised urine osmolality and high urine sodium concentration. Treatment requires fluid restriction, usually of 1 L/day. If intravenous fluids are required, only 0.9% saline should be used, to prevent a rapid increase in serum sodium. If the sodium is corrected too quickly, the patient may develop central pontine myelinolysis, which can cause severe and permanent neurological complications that can be fatal. Therefore, correction must occur over days, with regular assessment of serum sodium.

Answer 134

B – Carbimazole This young pregnant woman presents with thyrotoxicosis and ophthalmoplegia, features typical of Graves’ disease. The first-line treatment in the under-40s is carbimazole, a drug that inhibits the production of thyroid hormones. Iodine- 131 should be avoided in women who are pregnant or who are around children, due to the risk of radioactivity-induced teratogenicity.

Answer 135

I – Total thyroidectomy and thyroxine This woman has an enlarging asymptomatic thyroid lump with lymphadenopathy. It is most likely that she has a papillary thyroid cancer. This is managed by total thyroidectomy followed by daily thyroxine to help prevent recurrence of the tumour.

Answer 136

D – Hydrocortisone and fludrocortisone The features that this young girl has are typical of adrenal insufficiency. This, along with the recent meningococcal septicaemia, points to an underlying diagnosis of Waterhouse–Friderichsen syndrome, i.e. bilateral haemorrhage into the adrenal glands caused by meningococcal septicaemia. Management of adrenal insufficiency is by replacement of glucocorticoids (by hydrocortisone) and mineralocorticoids (by fludrocortisone).

Answer 137

B – Cryptococcus infection This man with HIV presents with features typical of meningitis. In cases of subacute meningitis in immunocompromised patients, one must be wary of Cryptococcus infection and tuberculosis. Cryptococcus neoformans is an encapsulated fungus found in soil, and infection is by inhalation of contaminated material. Cryptococcus is diagnosed by detection of capsular material (e.g. in cerebrospinal fluid or sputum) using India ink stain. Treatment is with intravenous amphotericin B. Cryptococcus infection can also result in pulmonary disease.

Answer 138

A – Candidiasis This woman with HIV infection, sore mouth, dysphagia and odynophagia has a Candida infection affecting her oesophagus. Diagnosis can be confirmed by endoscopy demonstrating white plaques typical of candidiasis. The presence of oesophageal candidiasis in anyone is highly suggestive of immunodeficiency. Treatment is with antifungals, such as fluconazole and amphotericin.

Answer 139

A – Abbreviated Mental Test Score The Abbreviated Mental Test Score (AMTS) is a quick and easily remembered way of initially and continuously assessing a patient’s cognitive function. It involves asking the patient 10 questions that assess several different areas of cognition. It is especially useful in elderly patients suffering from delirium and dementia. A score of less than 7/10 indicates cognitive impairment.

Answer 140

H – Rockall Score This scoring system can be used to predict adverse outcome following upper gastrointestinal bleeds by combining a number of independent risk factors (see below). A score >8 indicates a 40% risk of mortality.

Answer 141

I – Waterlow Score The Waterlow Score is an important tool for assessing the risk of pressure sore development. Pressure sores are likely to develop in bedbound patients who have poor mobility, poor nutrition, incontinence and multiple comorbidities. They can cause significant pain and become infected, leading to sepsis and even death. The Waterlow Score is generally used by nurses during the admission of patients, and is especially important in stroke victims, patients with quadriplegia and comatose patients.

Answer 142

J – Vertebrobasilar insufficiency In vertebrobasilar insufficiency, there is a temporarily reduced flow in the posterior circulation of the brain. It typically affects those aged 60–70 and reflects underlying atherosclerosis. Transient ischaemia in vertebrobasilar insufficiency is precipitated by neck extension, and results in dizziness.

Answer 143

D – Horner’s syndrome Horner’s syndrome is caused by an interruption of the sympathetic innervation to the eye. It is characterized by four features: a partial ptosis with ipsilateral anhidrosis (loss of sweating), enophthalmos (the impression that the eye is sunk in) and miosis (constricted pupil). Congenital Horner’s syndrome may be associated with heterochromia of the iris – a difference in colour between the two eyes. Causes of non-congenital Horner’s syndrome include Pancoast’s tumour (a tumour at the lung apex – as in this case), brachial plexus palsies, cervical rib, cluster headache and trauma to the base of the neck.

Answer 144

E – Marcus Gunn pupil A Marcus Gunn pupil is one that reacts poorly to light in comparison with the contralateral pupil. This is elicited on examination using the ‘swinging flashlight test’: when a pen torch is held towards the good eye, both pupils constrict (as they should), but when it is then held against the affected eye, both pupils appear to dilate. This is because the affected pupil does not perceive the light as well, and so constricts less compared with when the light is shone into the normal pupil – hence it appears to dilate. The Marcus Gunn pupil is characteristic of optic nerve lesions (e.g. optic neuritis or compression of the nerve by an aneurysm or tumour).

Answer 145

A – Argyll Robertson pupil Argyll Robertson pupils are bilateral small pupils that accommodate but do not react to light. They are a feature of neurosyphilis, but can also occur with diabetes mellitus.

Answer 146

E - CT scan First investigation should be CT or MRI, before colonoscopy. Looking for skip lesions, bowel wall thickening. Colonoscopy is the definitive test to diagnose Crohn's - looking for aphthous ulcers, hyperaemia, oedema, cobblestoning, skip lesions.

Answer 147

L – Tricuspid regurgitation Pulmonary hypertension can be primary or secondary to cardiac or systemic disease. Increased pressures in the pulmonary vasculature result in a backpressure that feeds back to the right ventricle. This causes the right ventricle to hypertrophy and dilate, which prevents the tricuspid valve cusps from opposing. Thus, blood is able to regurgitate from the right ventricle into the right atrium during systole. On auscultation, there is a pansystolic murmur that is best heard at the left sternal border in the fifth intercostal space. In severe disease, patients have a raised jugular venous pressure with a prominent v-wave, peripheral oedema and tender, pulsatile hepatomegaly.

Answer 148

E – Lupus nephritis Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of antinuclear antibodies. Up to 50% of patients with SLE have renal involvement. Proteinuria, hypertension, haematuria and peripheral oedema may all be seen. The renal damage is thought to arise from the deposition of immune complexes within the glomeruli that trigger an immunological response, damaging the basement membrane. A renal biopsy is usually required for the diagnosis and staging of the disease. The pattern of glomerulonephritis is mesangial, focal proliferative, diffuse proliferative or membranous. Lupus nephritis is treated by systemic immunosuppression using agents such as prednisolone, ciclosporin and mycophenolate. Some patients require renal replacement therapy and eventual renal transplantation.

Answer 149

A – AA amyloidosis In amyloidosis, there is deposition of extracellular fibrillar proteins in tissues and organs. The two main types of amyloidosis are AL and AA. AL amyloidosis, also incorrectly referred to as primary amyloidosis, is due to the clonal proliferation of plasma cells and particularly affects the cardiovascular system. AA amyloidosis, also known as reactive systemic amyloidosis, is due to the production and deposition of amyloid in chronic inflammatory conditions such as Crohn’s disease, rheumatoid arthritis and tuberculosis. In AA amyloidosis, amyloid A protein is deposited in the kidneys, liver and spleen, causing renal failure and hepatosplenomegaly. Cardiovascular involvement is rare. The renal complications of amyloidosis include proteinuria, nephrotic syndrome and endstage renal failure. Amyloidosis is traditionally diagnosed based on a biopsy of the affected tissue. The fibrillar protein shows green birefringence when stained with Congo red and examined beneath a polarised light. AL amyloidosis can be managed with chemotherapy or stem cell transplantation, but is usually fatal within 2 years. AA amyloidosis may respond to treatment of the underlying cause.

Answer 150

F – Staphylococcus aureus Intravenous drug users are at risk of developing bacterial endocarditis secondary to S. aureus bacteraemia introduced during non-sterile venepuncture. The valves that are affected tend to be (previously) normal and are often right-sided. In this case, the tricuspid valve is affected, causing significant regurgitation and right heart failure. The antibiotics of choice in acute S. aureus endocarditis are intravenous flucloxacillin and gentamicin. If resistant bacteria, such as meticillinresistant S. aureus (MRSA), are suspected or proven, intravenous vancomycin plus gentamicin should be initiated.

Answer 151

J – Viridans streptococcus Viridans streptococci are a large group of bacterial organisms that are usually commensals in the oral cavity. They are the most common cause of bacterial endocarditis, being responsible for approximately 60% of cases. Individuals with pre-existing valvular disease are at risk of viridans streptococcal endocarditis following invasive dental procedures such as tooth extraction. Antibiotic treatment is usually with intravenous benzylpenicillin, with the addition of gentamicin if resistant bacteria are present. Patients with known valvular heart disease should always receive prophylactic antibiotics prior to any invasive procedure.

Answer 152

H – Staphylococcus epidermidis This organism is a skin commensal. It commonly infects prosthetic valves and other indwelling foreign bodies such as peritoneal dialysis lines and venous lines. This is due to the bacterium’s ability to adhere to, and grow on, prosthetic surfaces. S. epidermidis should therefore be suspected in all patients with prosthetic valves who present with the signs and symptoms of bacterial endocarditis. Antibiotic therapy is with benzylpenicillin and gentamicin. If infection occurs within the initial weeks following valve replacement, an urgent surgical opinion should be sought.

Answer 153

K – Streptococcus pneumoniae S. pneumoniae is the most common cause of community-acquired pneumonia. It often affects young and middle-aged people, and presents as a rapid-onset illness with high fevers, rigors and pleuritic chest pain. The production of rustycoloured sputum (blood stained) is characteristic. Chest X-ray often shows lobar consolidation. Chlamydophila pneumoniae (previously known as Chlamydia pneumoniae) causes a mild pneumonia in younger people, and may be associated with sinusitis, pharyngitis and laryngitis. Chest X-ray shows small segmental infiltrates. Mycoplasma pneumoniae affects adolescents and young adults, and tends to cause epidemics in 3-year cycles. Patients often present with few chest signs, but can develop erythema nodosum, pericarditis and haemolytic anaemia. Chest X-ray shows patchy or lobar consolidation and hilar lymphadenopathy.

Answer 154

J – Staphylococcus aureus S. aureus often complicates an underlying viral pneumonia. Infection can arise from other foci, such as osteomyelitis. The characteristic feature is the X-ray finding of abscesses, seen as cavities with air–fluid levels.

Answer 155

I – Zollinger–Ellison syndrome Zollinger–Ellison syndrome describes peptic ulceration secondary to a gastrin secreting adenoma (gastrinoma). The adenoma is usually located in the pancreas, but can be found in the stomach or small bowel. Approximately 60% of gastrinomas are malignant and have the potential to metastasize to local lymph nodes and the liver. The unregulated secretion of gastrin simulates the parietal cells in the gastric antrum to produce excessive amounts of hydrochloric acid. This disrupts the gastric and duodenal mucosa, causing peptic ulceration. The acid can also denature pancreatic enzymes, such as lipase, resulting in malabsorption and chronic diarrhoea. Diagnosis is often based upon endoscopic identification of multiple peptic ulcers in association with a raised fasting serum gastrin level. Treatment involves high-dose protein pump inhibitors and surgical resection of the adenoma. Patients with Zollinger–Ellison syndrome associated with multiple endocrine neoplasia (MEN) type 1 often have multiple adenomas that are not suitable for resection. In this situation, the patient can usually be managed using a somatostatin analogue (e.g. octreotide), which decreases gastrin secretion. Metastatic disease necessitates systemic chemotherapy.

Answer 156

A – Carcinoid tumour Carcinoid tumours are serotonin-secreting neoplasms derived from the enterochromaffin cells of the gastrointestinal tract. They are usually found in the terminal ileum, appendix or rectum, but can occur in extraintestinal sites such as the bronchi, testes and ovary. If the tumour is limited to the gastrointestinal tract, the serotonin that is secreted enters the portal vein and is metabolized by the liver. If there are liver metastases, or if the primary tumour is extraintestinal, the secreted serotonin escapes hepatic metabolism and enters the systemic circulation, causing flushing, tachycardia, wheeze, diarrhoea, heart valve fibrosis and right heart failure. This is known as carcinoid syndrome. Diagnosis is based on the history and elevated levels of 5-hydroxyindole acetic acid (5-HIAA), a serotonin metabolite, in the urine. Management is by resection or, in widespread disease, symptomatic treatment with octreotide. Carcinoid tumours are slow growing so, even if disseminated disease is present, patients can live for many years.

Answer 157

D – Central scotoma A scotoma describes an area of visual field loss within a field of normal vision. The blind spot is an example of a scotoma that is present in every human. Pathological scotomata can be caused by problems of the retina or optic nerve, e.g. multiple sclerosis, optic nerve glioma, glaucoma and vascular lesions. A scintillating scotoma describes an area of flashing lights within the field of vision, often seen in migraine. This can take the form of zigzag lines, in which case it is known as a fortification spectrum.

Answer 158

F – Low-dose dexamethasone suppression test This patient could have glucocorticoid excess (Cushing’s syndrome), which can be diagnosed using the dexamethasone suppression test. This involves measuring a baseline serum cortisol level at 09:00 before giving 0.5 mg of dexamethasone (a synthetic glucocorticoid) four times daily for 48 hours. At 48 hours, the serum cortisol level is repeated. In healthy individuals, the dexamethasone suppresses cortisol secretion by negatively feeding back to the anterior pituitary gland and inhibiting ACTH release. In Cushing’s syndrome, the cortisol levels remain elevated and the test is positive. If the low-dose dexamethasone suppression test is positive, a high-dose dexamethasone suppression test can be performed to differentiate between Cushing’s syndrome caused by pituitary disease (Cushing’s disease) and Cushing’s syndrome caused by the ectopic secretion of ACTH from a non-pituitary tumour (e.g. small cell lung carcinoma). This test involves measuring a baseline serum cortisol level at 09:00 before giving 2 mg of dexamethasone four times daily for 48 hours and then measuring a repeat serum cortisol level. If the 48-hour cortisol level is significantly lower than the pre-test sample, it is likely that pituitary disease is responsible, since it is partially sensitive to negative feedback. If the cortisol is not suppressed at 48 hours, it is likely that ectopic ACTH secretion is occurring, since it is completely unresponsive to negative feedback.

Answer 159

D – Glucose tolerance test It is possible that this patient has acromegaly. Growth hormone (GH) opposes the action of insulin, resulting in high plasma glucose levels. Features of acromegaly include swelling of the hands and feet, lower jaw protrusion, macroglossia (large tongue), bitemporal hemianopia, carpal tunnel syndrome, hypertension, hyperglycaemia and cardiomegaly. In health, high plasma glucose levels feed back to suppress GH secretion. In acromegaly, there is autonomous secretion of GH, usually from a pituitary adenoma, that escapes the control of negative feedback. The glucose tolerance test can be used to help diagnose acromegaly. Failure to suppress GH levels to below 1 µg/L 2 hours after a 75 g oral glucose bolus is considered a positive result. Other investigations used in the diagnosis of acromegaly include insulin-like growth factor 1 levels and cranial MRI.

Answer 160

F – Neurofibromatosis type 1 Neurofibromatosis is an autosomal dominant disorder characterized by the development of multiple neurofibromas from the neurilemmal sheaths of central and peripheral nerves. There are two types: in type 1 (NF1, also known as von Recklinghausen’s disease), the mutation is on chromosome 17; in type 2 (NF2), the mutation is on chromosome 22. NF1 is the ‘peripheral form’, accounting for 70% of cases. Features include multiple cutaneous neurofibromas, café-au-lait patches (at least six), axillary freckling and fibromas on the iris (Lisch nodules). Affected patients are also at risk of developing scoliosis and neural tumours (e.g. phaeochromocytoma, acoustic neuromas). NF2 is the ‘central form’ and has few or no cutaneous lesion. Instead, patients develop bilateral neural tumours (acoustic neuromas, optic nerve gliomas and meningiomas). Acoustic neuromas are benign tumours of the Schwann cells of cranial nerve VIII. They can occur in conjunction with neurofibromatosis or as isolated tumours. Because of their close relationship to cranial nerves VII and VIII, acoustic neuromas can result in hearing loss, motor symptoms of the face and vertigo.

Answer 161

J – Syringomyelia Syringomyelia describes the presence of a fluid-filled cavity within the spinal cord, usually in the cervical segments. The expanding cavity disrupts spinothalamic neurons, resulting in sensory loss (pain and temperature) in the affected distribution. Syringomyelia may be associated with congenital herniation of the cerebellar tonsils (Arnold–Chiari malformation). The best investigation is MRI. Management is by surgical decompression of the syrinx.

Answer 162

K – Von Hippel–Lindau disease This man presents with a phaeochromocytoma and has a history of other tumours. Von Hippel–Lindau disease is caused by an autosomal dominant defect on chromosome 3. The syndrome is characterized by retinal and intracranial haemangiomas and haemangioblastomas, renal cysts, renal cell adenocarcinoma, pancreatic tumours and phaeochromocytoma.

Answer 163

C – Ataxia telangiectasia Ataxia telangiectasia is an example of a hereditary ataxia. It is autosomal recessive and presents in childhood with progressive ataxia and athetosis (slow writhing movements). It is associated with the presence of telangiectasias on the conjunctiva, cheeks and ears. Patients also have immunodeficiency and are significantly predisposed to lymphoma and leukaemia. Friedreich’s ataxia is an autosomal recessive condition that presents in adolescence with ataxia and muscle weakness, hearing loss, dysarthria and optic atrophy. It is also associated with diabetes mellitus and cardiomyopathy. Examination may reveal areflexia, scoliosis and pes cavus (high-arched feet). Affected people are often wheelchair bound by 20 years.

Answer 164

F – Felty’s syndrome Anaemia in RA has four main underlying causes. There can be an anaemia of chronic disease, which tends to cause a normochromic normocytic anaemia (although 25% of cases are associated with a hypochromic microcytic picture). There may be an autoimmune haemolysis associated with the disease process. Some drug treatments of RA can result in anaemia, especially non-steroidal antiinflammatory drugs and gold. The final reason is Felty’s syndrome. Felty’s syndrome is a triad of RA, splenomegaly and hypersplenism (which results in pancytopenia). Sequelae of pancytopenia include anaemia and recurrent infections. Felty’s syndrome is also associated with leg ulcers and lymphadenopathy. In some cases, splenectomy can improve symptoms.

Answer 165

H – Sensory ataxia Sensory ataxia occurs with a loss of joint position sense. Affected patients literally have to watch their feet, and they tend to place the foot on the ground with greater emphasis, especially in conditions of poor lighting. This can lead to stamping of the feet with walking (‘stomping gait’). Sensory ataxia occurs with disorders affecting the dorsal column of the spinal cord (which controls joint position sense and vibration). Causes include tabes dorsalis of neurosyphilis and vitamin B 12 deficiency (pernicious anaemia).

Answer 166

K – Waddling gait Difficulty standing from a sitting position and trouble walking up stairs is indicative of proximal muscle weakness (i.e. hip girdles). This is a known sideeffect of steroid use. If the muscles that stabilize the hip joint (the gluteus medius and minimus) are weak, the hips will not be fixed when the contralateral leg is lifted off the ground. This results in exaggerated trunk movements bilaterally, described as a waddling gait.

Answer 167

I – Spastic gait This child has cerebral palsy. The described deformity is characteristic of spasticity (hips adducted and internally rotated, knees flexed and ankles plantarflexed). In these circumstances, both lower limbs are moved slowly and dragged along the ground, with crossing of the legs due to adduction at the hip. Movement in the patient with bilateral spasticity is known as a scissoring gait.

Answer 168

M – Oxygen via facemask, nebulized short-acting β2-agonist and steroids This is a severe exacerbation of asthma. Features of severe asthma are: • the patient is too breathless to finish sentences • respiration rate ≥25/min • pulse ≥100 beats/min • peak flow ≤50% predicted or best. Acute exacerbations of asthma should be treated immediately with 60% oxygen (via a mask), back-to-back nebulizers and systemic steroids (either oral prednisolone or intravenous hydrocortisone). Patients should have their oxygen saturations measured continuously, and have regular PEFR readings (e.g. every 15–30 minutes) and serial arterial blood gases.

Answer 169

C – Posterior circulation stroke The classification of acute stroke was first described by Bamford and the Oxfordshire Community Stroke Project in the 1990s as follows. A total anterior circulation stroke (TACS) results in a triad of hemiplegia, hemianopia and higher cortical dysfunction (e.g. aphasia and visuospatial problems). A partial anterior circulation stroke (PACS) displays two of the above three features. A posterior circulation stroke (POCS) affects the brain stem, resulting in vertigo, dysphagia, dysarthria and facial weakness.

Answer 170

B – Partial anterior circulation stroke The classification of acute stroke was first described by Bamford and the Oxfordshire Community Stroke Project in the 1990s as follows. A total anterior circulation stroke (TACS) results in a triad of hemiplegia, hemianopia and higher cortical dysfunction (e.g. aphasia and visuospatial problems). A partial anterior circulation stroke (PACS) displays two of the above three features. A posterior circulation stroke (POCS) affects the brain stem, resulting in vertigo, dysphagia, dysarthria and facial weakness.

Answer 171

A – Lacunar stroke A lacunar stroke (LACS) is a pure motor stroke (hemiparesis), a pure sensory stroke or a combination of the two. The deficit in an LACS must involve two of the face, leg and hand. Furthermore, there must be no visual field defect, no higher cortical dysfunction, no brain stem disturbance and no drowsiness in an LACS.

Answer 172

D – Total anterior circulation stroke The classification of acute stroke was first described by Bamford and the Oxfordshire Community Stroke Project in the 1990s as follows. A total anterior circulation stroke (TACS) results in a triad of hemiplegia, hemianopia and higher cortical dysfunction (e.g. aphasia and visuospatial problems). A partial anterior circulation stroke (PACS) displays two of the above three features. A posterior circulation stroke (POCS) affects the brain stem, resulting in vertigo, dysphagia, dysarthria and facial weakness.

Answer 173

G - Pellagra Pellagra is a disorder caused by niacin (vitamin B3) deficiency. The main physical features are weakness, dermatitis and diarrhoea. There can also be personality changes, progressing to dementia. Treatment is with niacin. Death can occur within a few years if the condition is untreated.

Answer 174

K – Mesenteric ischaemia Mesenteric ischaemia is caused by atherosclerotic disease of the coeliac trunk and mesenteric arteries. Stenosis of the mesenteric arteries leads to inadequate perfusion of the bowel at times of increased oxygen demand, such as when digesting food. The condition usually presents with severe, griping abdominal pain 15–45 minutes after eating. Patients often fear to eat, because of the anticipation of pain, and can lose significant amounts of weight as a result. Mesenteric ischaemia must be differentiated from acute mesenteric infarction, which occurs when a local atherosclerotic plaque ruptures or when the artery becomes occluded by an embolus from a distant source, e.g. the left atrium in atrial fibrillation. Mesenteric infarction is extremely painful and typically lacks clinical signs. If it is suspected, an urgent surgical opinion is warranted.

Answer 175

I – Mycobacterium avium complex Mycobacterium avium complex (MAC) is a group of related airborne bacteria that includes Mycobacterium avium–intracellulare. Because of the low pathogenicity of these bacteria, clinical symptoms are usually found only in immunocompromised patients. Features are similar to those of tuberculosis: productive cough, shortness of breath, fever, lethargy, night sweats, weight loss, diarrhoea and abdominal pain. A chest X-ray may demonstrate the pulmonary MAC lesions. Sputum stain and culture can also help establish diagnosis. Treatment is with antituberculous drugs, including rifampicin, ethambutol and amikacin.

Answer 176

H – Synchronized DC cardioversion This patient with palpitations is in fast atrial fibrillation causing haemodynamic compromise. This is an emergency, and requires prompt action. Once the airway and breathing have been assessed and secured, the patient requires emergency DC cardioversion. DC cardioversion can be either synchronized (performed at a specific point of the cardiac cycle) or unsynchronized (done at any point, regardless of the cardiac cycle). In acute, unstable atrial fibrillation, shocks are synchronized with an R-wave on the ECG in order to reduce the chance of ventricular fibrillation. The patient needs to be adequately anticoagulated with intravenous heparin before the procedure, as cardioversion may precipitate systemic embolization from an intracardiac thrombus.

Answer 177

A - Adenosine This patient is experiencing a supraventricular tachycardia that is most likely to be an atrioventricular nodal re-entrant tachycardia (AVNRT) or atrioventricular re-entrant tachycardia (AVRT). The typical ECG findings are of a regular narrow complex tachycardia with no obvious P-waves. Provided that the patient is haemodynamically stable, the initial treatment is with vagal manoeuvres such as the Valsalva manoeuvre, and carotid sinus massage. The Valsalva manoeuvre, where the patient forcefully exhales against a closed epiglottis by blowing hard on a syringe, is the most commonly employed and safest vagal manoeuvre available. If such methods fail to slow the heart rate, or if the patient is haemodynamically compromised, they will require cardioversion. The first-line method in AVNRT and AVRT is chemical cardioversion with adenosine. Adenosine is given as an intravenous bolus of 6 mg, increasing to 12 mg if cardioversion does not occur. Before administrating adenosine, the patient should be placed on a cardiac monitor and warned that they will experience significant chest tightness and dyspnoea.

Answer 178

B – Cerebellar ataxia The examination features of spider naevi and gynaecomastia suggest significant alcohol use. This patient is also displaying features of cerebellar dysfunction (wide-based gait and past pointing), which can be a consequence of alcohol excess. ``` Cerebellar dysfunction results in a characteristic set of features summarized by the acronym DANISH: Dysdiadochokinesis Ataxia (wide-based gait) Nystagmus Intention tremor Slurred speech Hypotonicity. ``` Less severe degrees of cerebellar ataxia can be elicited by asking the patient to walk heel to toe.

Answer 179

C – Extrapyramidal gait This man has difficulty walking and controlling the speed of his gait. This is typical of an extrapyramidal gait seen in Parkinson’s disease. Patients find it difficult to initiate walking. They start with stuttering steps that quickly increase in frequency while decreasing in length (also known as a festinant gait). Patients with Parkinson’s disease may also get ‘stuck’ when walking though doors (‘freezing’).

Answer 180

I – Spastic gait This man has recently had a stroke causing a right-sided spastic hemiparesis. This results in a gait where the upper limb is held in flexion, the hip in extension and the ankle plantarflexed. Patients with spastic hemiparesis find that they need to swing their affected leg out from the hip (circumduction) to prevent it from scuffing the ground on walking. Cerebral palsy causes diplegic gait (scissoring) which is when this happens with both legs.

Answer 181

A – Anti-centromere This is the limited cutaneous form of systemic sclerosis (scleroderma) - previously known as CREST syndrome - with skin thickening confined to sites distal to the elbows and knees, but can also involve the face. 5 CREST features are: Calcinosis, Raynaud's, oEsophageal dysmotility, Sclerodactyly (skin fibrosis on fingers), Telangiectasia Associated with ANA, anti-centromere (limited form only) antibodies & Rhematoid factor. DIFFUSE cutaneous systemic sclerosis: skin thickening on the proximal limbs or the trunk in addition to face and distal extremities. Anti-Scl 70 (anti-topoisomerase) is more associated with the DIFFUSE form, with ANA

Answer 182

C – Anti-Jo-1 Dermatomyositis here, but anti-Jo-1 is more commonly found in polymyositis. General ANA are found in both.

Answer 183

B – Anti-dsDNA SLE, also associated with anti-Smith and ANA (most sensitive) antibodies. Anti-Smith and anti-dsDNA are both specific for SLE.

Answer 184

H – cANCA (Wegener's) granulomatosis with polyangiitis.

Answer 185

G – Anticardiolipin Antiphospholipid syndrome, also associated with Anti-beta2-glycoprotein I antibody. Hx of vascular thrombosis, pregnancy loss, SLE, arthritis, thrombocytopaenia.

Answer 186

I – Multiple endocrine neoplasia type 1 This young patient has multiple peptic ulcers, which are suggestive of a gastrinoma, a pancreatic tumour. The brain tumour that causes lactation is a prolactinoma, a tumour of the pituitary gland. The combination of pancreatic endocrine tumours with a gastrinoma suggests multiple endocrine neoplasia (MEN) type I. There are three types of MEN, all of which are autosomal dominant conditions. MEN type 1 (Wermer’s syndrome) includes the presence of parathyroid adenomas, pancreatic islet cell tumours and pituitary adenomas. MEN type 2A (Sipple’s syndrome) comprises parathyroid adenomas, medullary carcinoma of the thyroid and phaeochromocytoma. Finally, MEN type 2B (which has in the past been termed ‘MEN type 3’) includes the presence of the tumours of MEN type 2A with the addition of multiple mucosal neuromas of the gastrointestinal tract and a marfanoid phenotype.

Answer 187

E – Conn’s syndrome This woman presents with polyuria, polydipsia and muscle cramps associated with a high sodium and a low potassium. This suggests a diagnosis of Conn’s syndrome. Conn’s syndrome results from an aldosterone-secreting adenoma of the adrenal gland. Aldosterone causes sodium reabsorption and potassium excretion in the kidneys. Excess aldosterone results in sodium and water retention, leading to high blood pressure and oedema. Excess potassium excretion results in hypokalaemia, the features of which include muscle cramps and weakness, polyuria (secondary to renal tubular damage, i.e. nephrogenic diabetes insipidus) and polydipsia. The diagnosis of Conn’s syndrome can be made by measuring serum aldosterone and renin levels – aldosterone will be raised and renin levels will be reduced due to negative feedback. It should be noted that many antihypertensive medications interfere with these hormones, so it is important to stop these for at least 6 weeks before testing. Initial management is with spironolactone, an aldosterone antagonist. Once the adenoma has been localized (using CT), it can be surgically removed.

Answer 188

K – Multiple endocrine neoplasia type 2B This patient is likely to have MEN type 2B, an autosomal dominant condition characterized by phaeochromocytoma, parathyroid adenomas, medullary thyroid cancer, multiple mucosal neuromas and a marfanoid habitus (e.g. tall, arachnodactylyl, high-arched palate).

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