PASTEST Flashcards

Question

An 81-year-old woman is admitted with bowel obstruction, pain and dehydration. An abdominal radiograph is performed by the admitting doctor with features suggesting volvulus of the large bowel. What is the commonest form of volvulus in the elderly? 1) Caecal 2) Sigmoid 3) Small bowel 4) Stomach 5) Transverse colon

Answer 1

Explanation Sigmoid Volvulus occurs when a segment of bowel twists on its mesentery. Sigmoid volvulus is the commonest form of volvulus in the elderly and occurs in an anticlockwise direction. It is seen in approximately 5% of cases of large bowel obstruction in developed countries. The characteristic radiological appearance is known as a ‘coffee bean’ which arises from the left iliac fossa. The volvulus may be resolved by passing a flatus tube and, if unsuccessful, more aggressive surgical management. Caecal Caecal volvulus is less common than volvulus of the sigmoid colon. Small bowel A small bowel volvulus is rare; more commonly obstruction of the small bowel is due to adhesions from previous surgery. Stomach Gastric volvulus is uncommon and can occur at any age but a higher incidence is seen in the elderly. Transverse colon Again, this is an uncommon form of volvulus.

Answer 2

Explanation Metabolic acidosis Metabolic acidosis can be due to impaired hydrogen excretion, increased hydrogen ion production or ingestion, or loss of bicarbonate. In this patient, the rapidly spreading cellulitis coupled with significant cardiovascular compromise could indicate necrotising fasciitis and should be suspected. The acidosis is likely due to a diabetic ketoacidosis; diabetes is also a risk factor for necrotising fasciitis. Other causes of metabolic acidosis include renal disease, lactic acidosis, salicylate poisoning and chronic diarrhoea and intestinal fistulas. Metabolic alkalosis Given the severe infection and diabetes a metabolic acidosis, not alkalosis, is likely. Mixed metabolic alkalosis with respiratory compromise Metabolic alkalosis with respiratory compensation would be unlikely. Respiratory compensation would be through hypoventilation, and given this patient is haemodynamically unstable and septic it is likely he would be tachypneic. Additionally, sepsis causes a metabolic acidosis due to anaerobic respiration. Respiratory acidosis A respiratory acidosis would occur in the presence of hypoventilation. This patient is likely to have a high respiratory rate due to sepsis. Respiratory alkalosis This occurs during hyperventilation as more carbon dioxide is ‘blown off’ causing a reduction in hydrogen ions. Carbonic anhydrase in erythrocytes facilitates a reaction between carbon dioxide and water that results in hydrogen ions. As such, a reduction in carbon dioxide, through hyperventilation, will reduce the number of hydrogen ions and so acidity. The primary issues for this patient however is a metabolic acidosis due to sepsis.

Answer 3

Explanation Intravenous fluids Hypercalcaemic crisis occurs when a patient with mild hypercalcaemia has a rapid rise in plasma calcium. This is associated with rapid deterioration in the patient’s condition, in the form of confusion, drowsiness, vomiting and dehydration. The first-line treatment of hypercalcaemia is intravenous fluid replacement with 0.9% saline. Crises may be precipitated by intercurrent illness, operation or infection. Intravenous magnesium This has no role in the treatment of a hypercalcaemic crisis. Steroids Hypercalcaemic crises due to hyperparathyroidism do not respond to treatment with steroids. Even in hypercalcaemia of different aetiologies, corticosteroids are considered second-line treatment. Calcitonin The condition may be controlled pre-operatively by the careful use of calcitonin or mithramycin but these would not be initial treatment. Intravenous phosphate Sodium phosphate infusion is dangerous; it lowers the calcium concentration rapidly, but risks causing metastatic calcification.

Answer 4

Explanation Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is a life-threatening condition associated with significant morbidity and mortality, yet with early recognition and management these can be improved greatly. As such, in recent years there has been a concerted effort to improve the recognition and management of sepsis which includes increasing public awareness and producing a clear definition of sepsis. Recent National Institute of Clinical Excellence (NICE) Guidance was released in 2016 in response to a UK Parliamentary inquiry examining sepsis. The ‘Time to Act’ report found failures in the recognition, diagnosis, and early management of those who died from sepsis. Part of this guidance was clarifying the definition of sepsis as previously there was a confusing mix of terminology being used to describe the disease process, including; septicaemia, sepsis, septic shock and systemic inflammatory response syndrome (SIRS). Efforts are now being made to improve the recognition, diagnosis and management of sepsis throughout the UK. The presence of bacteria in the bloodstream This simply describes a bacteraemia that may or may not be related to sepsis depending if there is organ dysfunction or a dysregulated host response to infection. The presence of micro-organisms within a normally sterile viscus Sepsis is a systemic dysregulated response to infection and is not limited to a viscus. Hypotension refractory to resuscitation in the presence of demonstrable infection In the past this would have been referred to as septic shock. A universal definition of sepsis is now in use and terminology such as septic shock should be avoided and replaced simply with sepsis. Low blood pressure, signs of fluid overload and the presence of a proven source of infection. This is not the universally agreed definition of sepsis.

Answer 5

Explanation Sepsis is a well recognised cause There are several causes of multi-organ dysfunction syndrome, however infections (resulting in sepsis) and injuries (either trauma or surgery) are the most common causes. If sepsis is left untreated, or unrecognised, then this can progress to septic shock and multi-organ dysfunction syndrome. Jaundice is usually due to gallstones Intrahepatic cholestasis and hepatocyte necrosis is the usual cause of jaundice in these patients. Mortality rates are low Multi-organ dysfunction syndrome unsurprisingly is associated with a high mortality rate, approximately 30–100%. There is a decreasing alveolar–arterial oxygen gradient A decreasing alveolar–arterial (A–a) gradient implies there is a reduced diffusion barrier to Ocrossing from the alveolus to 2 blood and would enhance gas transfer. In ARDS the A–a gradient increases due to alveolar–capillary membrane thickening caused by endothelial leakage and accumulation of interstitial fluid. There is increased lung compliance Increased lung compliance means the lung is more distensible so that a smaller fall of intrapleural pressure would be required for a given tidal volume during inspiration and respiratory work would decrease (in emphysema this is a problem as expiratory recoil is reduced). In ARDS lung compliance is reduced. In multiple organ dysfunction syndrome there is an uncontrolled inflammatory response and mal-distribution of blood flow, as a result of microembolic phenomenon, excessive release of various vasoactive compounds (vasoconstrictors, vasodilators and those that increase capillary permeability) which leads to interstitial oedema and a mismatch between supply and demand for oxygen within the microcirculation. Other hypotheses include inappropriate and uncontrolled release of cytotoxic mediators from bacteria.

Answer 6

Explanation Initiate nursing in a prone position Nursing in a prone or seated position has been shown to improve refractory hypoxaemia caused by ARDS. Close monitoring within a level 1 care facility Patients should be managed in a level 2 or level 3 facility, which refers to an acute district hospital (level 2) or level 3 which is a tertiary referral centre (usually a teaching hospital). A level 1 care facility refers to a community hospital. Computed tomography (CT) scan This patient is critically unwell and a CT scan is unlikely to change current management; she primary requires treatment for ARDS and pancreatitis. Furthermore, transfer to the radiology department carries inherent risk for limited benefit. Dopamine therapy to support renal function Dopamine is not recommended as it has been shown to cause arrhythmias, so should be avoided. Early endoscopic retrograde cholangiopancreatography (ERCP) This patient is critically unwell and in their current condition ERCP is extremely risky. Early ERCP is only recommended for patients with co-existing cholangitis or biliary obstruction.

Answer 7

Explanation Intramuscular adrenaline The principles of management of severe anaphylactic shock include: airway maintenance and oxygen; intravenous fluids to provide circulatory support; and subcutaneous or intramuscular adrenaline (adrenaline). The dose for an adult is 0.5 mg adrenaline, repeated after 5 min as required. Subsequent treatment is with an anti- histamine (chlorphenamine 4 mg) and corticosteroid (hydrocortisone 100 mg), however, adrenaline should be given first as this is the life-saving treatment. Nebulised bronchocdilators Nebulised bronchodilators can help counteract the bronchospasm, however, intramuscular adrenaline is the primary treatment. Beta blockers Beta blockers are contraindicated as they lower blood pressure and may cause bronchoconstriction, so have no role in the treatment of anaphylaxis. Intravenous nitrates Intravenous nitrates cause vasodilation and have no role in the treatment of anaphylaxis. Intravenous morphine Intravenous is primarily reserved for severe pain management, therefore would not be indicated in the treatment of anaphylaxis.

Answer 8

Explanation Endotoxins act as a negative inotrope Endotoxins act as a negative inotrope and can initiate both ARDS and disseminated intravascular coagulation (DIC). Tissue uptake of oxygen by cells is normal Tissue uptake of oxygen by cells is reduced, contributing to the metabolic acidosis of sepsis due to anaerobic respiration and so increased lactic acid production. Peripheral vasoconstriction is seen Peripheral vasodilation is seen throughout the systemic circulation causing reduced tissue perfusion and organ dysfunction if not treated. Blood cultures are commonly positive Blood cultures are rarely positive, however, if the causative bacteria is grown from blood cultures then this significantly aids treatment as targeted antimicrobial therapy is possible. Gram-negative organisms are the most common cause Septicaemic shock is most commonly due to Gram-positive organisms. While Gram- negative bacteria were previously considered the most common cause of septic shock, recent epidemiological studies revealed approximately 200 000 cases of Gram-positive sepsis annually, compared with 150 000 cases of Gram-negative sepsis in recent years. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–54.

Answer 9

Explanation It is characterised by decreased lung compliance. Pulmonary fibrosis in the later stages of the disease leads to a decrease in the functional residual capacity, further decrease in lung compliance, and an increase in the shunt effect. It has an increased pa (O2 ) (in mmHg) to FI O 2 ratio. ARDS is characterised by refractory hypoxemia (pa (O2 ) < 8 kPa at FI O 2 > 0.4), alveolar inflammation and oedema, reduced total compliance (< 30 ml/cmH2 O) and a pa (O2 ) (in mmHg) to FI O 2 ratio of < 200 (normal is approximately 500). It has < 20% mortality in established cases. The mortality of this condition is as high as 50–70%. It is caused due to collapse of the alveoli. Indirect or direct lung injury initiates abnormal behaviour and movement of neutrophils, platelets and macrophages. Neutrophils and platelets attach to capillary endothelium causing capillary leak. This leads to oedema of lung tissue and movement of neutrophils and erythrocytes into the lung parenchyma. Lung lymph flow is increased and there is thickening of the alveolar–capillary membrane. This results in impaired oxygen diffusion and reduced lung compliance as the alveolus is surrounded by fluid. In addition, some of the fluid in the pulmonary parenchyma may leak into the alveoli, giving the characteristic appearance of a hyaline membrane. It usually develops in the first 24 h after injury. ARDS can present as soon as 2 h following injury. ARDS is an acute, diffuse inflammatory process resulting from direct or indirect pulmonary injury. It is most commonly seen in sepsis but can also occur after trauma, burns, inhalation injuries, shock and pancreatitis. In post-operative surgical patients, abdominal sepsis or central- line sepsis should be considered. Pulmonary signs are often minimal or non-specific, the patient simply being breathless, progressively tachypneic, hypoxic and then cyanotic. Chest X-ray may be normal in the early stages but later shows bilateral diffuse pulmonary infiltration. Treatment, in addition to eliminating the precipitating cause, involves ventilating the patient in an Intensive Care Unit. Patients are usually nursed in the prone position. The tidal volume should be kept low (approximately 6 ml/kg) and so should the pulmonary capillary wedge pressure (high pressures exacerbate pulmonary oedema).

Answer 10

Explanation Abdominal sepsis ARDS is an acute diffuse inflammatory process resulting from direct or indirect pulmonary injury. It is most commonly seen in sepsis but can also occur after trauma, burns, inhalation injuries, shock and pancreatitis. In post-operative surgical patients, abdominal sepsis or central-line sepsis should be considered. Pulmonary signs are often minimal or non-specific in the early stages, the patient simply being breathless, but, if untreated, they could soon become hypoxic and cyanotic. Chest X-ray may be normal in the early stages but later shows bilateral diffuse pulmonary infiltration. The mortality of this condition is as high as 50–70%. Fat embolism Fat embolism is a recognised complication of long bone fractures which are associated with major trauma. As described above, major trauma can cause ARDS, however, given this patient has been treated for peritonitis, abdominal sepsis is the most likely cause. Pancreatitis Pancreatitis is a recognised cause of ARDS, however abdominal sepsis is more likely given the case history. Pulmonary fibrosis Pulmonary fibrosis occurs as a result of ARDS. Fibrosis in the later stages of the disease leads to a decrease in the functional residual capacity, further decrease in lung compliance and an increase in the shunt effect. Trauma As mentioned, major trauma is a recognised cause of ARDS, however, abdominal sepsis is the likely cause in this patient. ARDS is characterised by refractory hypoxaemia (pa (O2 ) < 8 kPa at Fi O2 > 0.4), alveolar inflammation and oedema, reduced total compliance (< 30 ml/cm water) and a pa (O2 ) (in mm Hg):Fi O 2 ratio of < 200 (normal is approximately 500). Indirect or direct lung injury initiates abnormal behaviour and movement of neutrophils, platelets and macrophages. Neutrophils and platelets attach to capillary endothelium causing capillary leakage. This leads to oedema of lung tissue and movement of neutrophils and erythrocytes into the lung parenchyma. Lung lymph flow is increased with thickening of the alveolar–capillary membrane. This results in impaired oxygen diffusion and reduced lung compliance as the alveolus is surrounded by fluid. In addition, some of the fluid in the pulmonary parenchyma may leak into the alveoli, giving the characteristic appearance of a hyaline membrane. Treatment, in addition to eliminating the precipitating aetiology, involves ventilating the patient in intensive care. Patients are usually nursed in the prone position. The tidal volume should be kept low (approximately 6 ml/kg), as should the pulmonary capillary wedge pressure (high exacerbates pulmonary oedema).

Answer 11

Explanation Leakage of protein rich oedema fluid into the lung tissue The underlying pathological process is leakage of cells and fluid through the capillary walls of the alveoli. The alveolar membrane thickens and ultimately fibroses. Focal infiltration on chest X-ray Typically the chest X-ray shows diffuse infiltration. Only late occurrence of tachypnoea and tachycardia In the early stages, tachycardia and tachypnoea may be the only features. Later there is cyanosis and worsening dyspnoea. Steroids promote recovery in the late phase Steroids have been used in the treatment of ARDS but there is no good evidence to support their use. The cornerstones of treatment are support of the circulation, respiratory support by ventilation and the use of appropriate antibiotics. Thinning of the alveolar membrane As mentioned thickening of the alveolar membrane occurs, and in the later stages of the disease, fibrosis occurs. Acute respiratory distress syndrome (ARDS) is a well recognised complication of sepsis, trauma and other pulmonary insults, both direct and indirect. The commonest clinical signs are tachypnoea, tachycardia, cyanosis and high-pitched coarse crepitations on auscultation. The alveolar membrane becomes thickened. Differential diagnoses include left ventricular failure, bronchitis, pneumonia and asthma.

Answer 12

Temperature of 38.0°C, a leucocyte count of 2x10 9 /l, respiratory rate 30 breaths/min Pyrexia, leucopenia and tachypnoea are all consistent with SIRS. A patient is said to have SIRS if they satisfy two or more of the following criteria: *temperature > 38°C or < 36°C *heart rate > 90 beats/min *respiratory rate > 20/min (or pa (CO2 ) < 32 mmHg) *leucocyte count > 12 000/mm 3 or < 4000/mm 3 [or > 10% immature (band) cells]. *Temperature of 37.5°C, a leucocyte count of 11 000/mm 3 , heart rate 150 beats/min This patient is normothermic, has a leucocyte count in the higher range of normal, and a significant tachycardia, as such they do not fit the criteria for SIRS. Temperature of 38°C, a leucocyte count of 5x10 9 /l, respiratory rate 15 breaths/min These parameters do not fill the criteria for SIRS. Temperature of 35.5°C, a leucocyte count of 8x10 9 /l, pa (CO2 ) 50 mmHg The low temperature fulfils the criteria, however, the leucocyte count is within the normal range (leucocyte count: 4–11 × 10 9 /l), and the pa (CO2 ) is satisfactory. Temperature of 37.5°C, a leucocyte count of 11x10 9 /l, heart rate 100 beats/min Only the tachycardia would satisfy the SIRS criteria.

Answer 13

Explanation Urine output < 0.5ml/kg/h for more than 2 h Decreased urine output is an indicator of reduced renal perfusion, which can be used as a surrogate marker for reduced generalised tissue perfusion. This is therefore maybe a sign of septic shock as it represents renal dysfunction which occurs in severe circulatory abnormalities or circulatory collapse. Post-splenectomy sepsis can present 20 years after splenectomy and carries a high mortality. It is prevented by penicillin prophylaxis. The micro-organisms most likely to lead to infection include pneumococcus and meningococcus species and H. influenzae. Other infections include those due to Escherichia coli and Plasmodium (malaria). The Surviving Sepsis Campaign has published international guidelines on the recognition and management of severe sepsis in an attempt to decrease the high mortality rates. Although NICE guidance lists ‘red- flags’ for sepsis (see below), the National Early Warning System (NEWS) introduced by the Royal College of Physicians is an alternative. Red-flags for sepsis according to NICE Guidelines: *systolic blood pressure <90 mmHg (or >40 mmHg fall from baseline) *heart rate >130 beats per min *oxygen saturations <91% *respiratory rate >25 breaths per min *responds only to voice or pain/unresponsive *lactate >2.0 mmol. Confirmed or suspected infection A patient can have an ongoing infection but may not have sepsis which is defined as ‘life-threatening organ dysfunction due to a dysregulated host response to infection’. Core temperature < 36°C or > 38.3°C Although temperature is commonly used as an indicator of infection, it is not a helpful indicator of either severe sepsis or septic shock. Septic shock is defined as ‘a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality’ – The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). It indicates a patient who is septic with refractory hypotension when given an intravenous fluid challenge/bolus. While sepsis is referred to as life-threatening organ dysfunction due to a dysregulated host response to infection, so a patient may have an infection causing pyrexia but may not have sepsis. Heart rate higher than 90 beats per min Heart rate can be used as a ‘red-flag’ sign for sepsis according to NICE guidance, however, it suggests a tachycardia above 130 beats per min. Respiratory rate higher than 20 breaths per min Again, NICE guidance suggests a ‘red-flag’ sign for sepsis is a respiratory rate above 25 breaths per min.

Answer 14

The most appropriate principle regarding the choice of intravenous fluid for resuscitation in a patient with septic shock is: 1) Certain intravenous solutions, which would be hypo-osmolar, have dextrose added to ensure they are iso-osmolar Explanation: In the context of intravenous fluid resuscitation for septic shock, the principles involve understanding the properties and functions of different types of fluids. Here’s a breakdown of the options: 1. Certain intravenous solutions, which would be hypo-osmolar, have dextrose added to ensure they are iso-osmolar: This is correct. Solutions like 5% dextrose are isotonic and provide free water once dextrose is metabolized, helping to ensure fluids remain iso-osmolar to avoid causing cellular dehydration or overhydration. 2. Hartmann’s solution contains sodium, potassium, chloride, calcium, and bicarbonate: This is incorrect. Hartmann’s solution (or Ringer’s lactate) contains sodium, potassium, chloride, calcium, and lactate (which is metabolized to bicarbonate), but not bicarbonate directly. 3. An advantage of crystalloid solutions is that relatively small volumes have to be infused to restore an intravascular volume deficit: This is incorrect. Crystalloids generally require larger volumes compared to colloids to achieve the same intravascular volume expansion due to their distribution across the extracellular space. 4. The normal colloid oncotic pressure is 70 mmHg: This is incorrect. Normal colloid oncotic pressure (oncotic pressure) is around 25-30 mmHg, not 70 mmHg. 5. Albumin is indicated: This is incorrect as a blanket statement. Albumin is a colloid and can be used in specific situations, but it is not the first-line treatment for fluid resuscitation in septic shock due to its cost and lack of evidence showing superiority over crystalloids. Correct Answer: 1) Certain intravenous solutions, which would be hypo-osmolar, have dextrose added to ensure they are iso-osmolar

Answer 15

Explanation 40% The mortality risk for a patient scoring 5 on the modified Glasgow score is 40%. The following criteria are used to calculate the score. 2% This would represent the mortality risk for a patient with a modified Glasgow score of 0–2. 15% This would represent the mortality risk for a patient with a modified Glasgow score of 3–4. 30% The mortality risk for a patient scoring 5 on the modified Glasgow score is greater than 30%. 100% Mortality risk reaches 100% when the patient scores between 7 and 8 on the modified Glasgow score. Pancreatitis is a common presentation in the UK, of which gallstones and alcohol are the two primary aetiologies. Gallstones account for up to 50% of pancreatitis in the UK, while alcohol accounts for 20–25%. The modified Glasgow score takes into account a number of parameter taken within the first 48 h following admission which can then be used to assess mortality risk These criteria are as follows; pa (O2 ) < 60 mmHg; age > 55 years; neutrophils > 15 × 10 9 /l; calcium < 2 mmol/l; raised urea > 16 mmol/l; enzyme (LDH) > 600 units/l; albumin, 32 g/l; sugar (glucose) > 10 mmol/l.

Answer 16

Explanation Serum amylase activity of 1244 U/l (upper limit of normal, 150 U/l) Patients in DKA often have elevated serum amylase activities as a result of decreased renal excretion of the enzyme, however, a level this high is very suggestive of pancreatitis and coupled with the epigastric pain, pancreatitis is the likely precipitant cause of his DKA. Serum creatinine concentration 140 µmol/l (normal value creatinine: 50–120 µmol/l) Serum creatinine concentration is often slightly raised in patients with DKA (even in the absence of diabetic nephropathy) as a result of dehydration and subsequently a decreased glomerular filtration rate. Serum lactate concentration 4.3 mmol/l (normal value lactate: 0.5–2.2 mmol/l) Decreased tissue perfusion as a result of dehydration often leads to an element of lactic acidosis secondary to anaerobic respiration, in addition to the ketoacidosis. Serum triglyceride concentration 12.2 mmol/l (normal value triglycerides: 0–1.5 mmol/l) Hypertriglyceridaemia is common in uncontrolled diabetes. White cell count of 15 × 10 9 /l (normal value WCC: 4–11 × 10 9 /l) An increased white cell count can occur in any acute illness and does not specifically indicate infection.

Answer 17

Explanation Adrenaline (epinephrine) During the metabolic response to trauma, there is increased secretion of catecholamines (such as adrenaline), cortisol, glucagon and growth hormone. Adrenaline acts most rapidly through stimulation of glycogenolysis causing blood glucose concentration to rise Cortisol Increased secretion of cortisol following trauma will increase blood glucose concentration, however, this occurs more slowly through the stimulation of gluconeogenesis. C-reactive protein C-reactive protein is an acute phase reactant and a marker of inflammation, but does not affect glucose homeostasis. Growth hormone Growth hormone is also released in response to major trauma. It can increase blood glucose concentration indirectly as it appears to potentiate the action of cortisol and opposes the action of insulin. Insulin Insulin is a hypoglycaemic hormone, therefore would lower blood glucose concentration.

Answer 18

Explanation Mallory-Weiss tear A Mallory–Weiss tea is a tear in the mucosal lining of the oesophagus that classically occurs after heavily vomiting (often following an alcohol binge as described in the case history). Most cases of bleeding from this are self-limiting and usually minor. Aortic-enteric fistula Aortic-enteric fistulae occur mostly following abdominal aortic aneurysm (AAA) repair in which communication has developed between the aorta and the small bowel. They result in very heavy blood loss into the small bowel and are often fatal. Boerhaave syndrome Boerhaave syndrome is perforation of the oesophagus secondary to vomiting. It is associated with a high morbidity and mortality, and would present with severe chest pain, fever and shock. The patient described in the case is not significantly unwell. Oesophageal varices Oesophageal varices are the result of portal hypertension as blood is shunted through arteriovenous anastomosis due to increased vascular resistance within the liver, most commonly as a result of cirrhosis secondary to alcohol. It would be rare for an 18-year- old to have significant liver cirrhosis to cause varices. Furthermore, variceal bleeding would be profuse, and unlikely to present with just streaks of blood in the vomit. Peptic ulcer disease A peptic ulcer can cause upper gastrointestinal bleeding, however, it would be unlikely in a young adult, and does not fit with the case history.

Answer 19

Explanation Aortic-enteric fistula Aortic-enteric fistulae occur mostly following abdominal aortic aneurysm (AAA) repair in which a communication has developed between the aorta and the small bowel. They result in very heavy blood loss into the small bowel and are often fatal. Angiodysplasia Angiodysplasia is the most common vascular lesion of the gut. Lesions are often multiple and presentation insidious, and may simply present as anaemia. Diverticular disease Diverticular disease may present with small amount of fresh PR bleeding, but given the proximity to surgery, an aortic-enteric fistula is more likely. Gastric Cancer Gastric cancer is likely to have a more insidious presentation. Again, as the bleeding would be upper gastrointestinal in nature, it would present as melaena not fresh blood. Peptic ulcer disease Peptic ulcer can cause bleeding, however this is likely to present as upper gastrointestinal bleeding. Occasionally, they can present as lower gastrointestinal bleeding but this will present as melena as opposed to fresh PR blood.

Answer 20

Explanation Primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a condition in which inflammation, fibrosis and Strictures of the intrahepatic and extra-hepatic bile ducts occur. MRCP shows multiple strictures in the biliary tree and a characteristic ‘beaded’ appearance. Around 80% of patients with PSC will have a diagnosis of UC. Cholangitis Cholangitis is an ascending infection of the biliary tree, given this patient has no signs of infection this is unlikely. Furthermore, strictures would not be seen in cholangitis. Cholecystitis This refers to inflammation of the gallbladder, most common caused by gallstones. If the gallstones become lodged in the common bile duct then obstructive jaundice may be seen, however, the finding of strictures on MRCP is more suggestive of primary sclerosing cholangitis. Primary biliary cirrhosis Primary biliary cholangitis is an autoimmune disorder causing destruction of the small interlobular bile ducts, subsequent intrahepatic cholestasis causes fibrosis and ultimately cirrhosis of the liver. The patient has a history of UC, so primary sclerosing cholangitis is a more likely, furthermore, strictures in the biliary tree would not be seen on MRCP. Wilson’s disease Wilson’s disease is a rare inherited disorder of copper metabolism leading to a pathological accumulation of copper within various organ, particularly affecting the liver and brain. Presentation is usually in teenager years with either neuropsychiatric conditions due to accumulation of copper in the brain, or with coagulopathy and hepatic encephalopathy from accumulation in the liver. As such, this does not fit with the case history given.

Answer 21

Explanation Rovsing’s sign Rovsing’s sign describes pain in the RIF more than the LIF when the LIF is pressed, and is a sign of appendicitis. Aaron’s sign Aaron’s sign is pain referred to the epigastrium upon continuous firm pressure over McBurney’s point and is indicative of appendicitis. Dunphy’s sign Dunphy’s sign is a medical sign in which increased abdominal pain occurs with coughing and is often present in appendicitis. Murphy’s sign Murphy’s sign occurs when pressing over the right upper quadrant (RUQ) with two fingers and asking the patient to breathe in, causes pain and arrest of inspiration as the inflamed gall-bladder impinges on the examiner’s fingers. It is only positive if repeating the test on the left does not result in a similar pain. Rigler’s sign Rigler’s sign is a radiological sign in which air is seen on an abdominal X-ray on both sides of the intestine.

Answer 22

Explanation Femoral hernia Femoral hernias classically emerge below and lateral to the pubic tubercle, and are more common in women due to the wider pelvis. As the neck for femoral hernias is relatively narrow and stiff, they are more likely to obstruct and strangulate. Epigastric hernia Given the patient has a lump in their groin, an epigastric hernia would be unlikely. Direct inguinal hernia Inguinal hernias emerge from above and medial to the pubic tubercle. Direct inguinal hernias pass through Hasselbach’s triangle directly through a defect in the anterior abdominal wall. Indirect inguinal hernia Again, inguinal hernias emerge from above and medial to the pubic tubercle, however, indirect inguinal hernias pass through the inguinal canal. Obturator hernia An obturator hernia is rare but is more common in women and twice as common on the right side. It particularly affects elderly women who have had recent rapid weight loss. The hernial sac protrudes through the obturator canal potentially compressing the geniculate branch of the obturator nerve causing referred pain. Given their anatomical location they are difficult to diagnose clinically and does not present as a lump in the groin.

Answer 23

Explanation Oesophageal rupture Oesophageal rupture (Boerhaave syndrome) occurs mostly either secondary to trauma eg during endoscopy or due to forceful vomiting. Excessive vomiting may be due to alcohol or in patients with a history of excessive eating and forced vomiting eg due to bulimia as suggested in this case. Perforation of the oesophagus causes a mediastinitis and an early diagnosis is crucial. Patients will deteriorate rapidly with systemic inflammatory response syndrome, unless the perforation is minimal. In patients with a significant perforation, resuscitation with surgery to debride the mediastinum and place a T-tube within the oesophagus is needed in most cases. Achalasia This refers to oesophageal dysmotility secondary to failure of smooth muscle of the lower oesophageal sphincter to relax during swallowing. It causes progressive dysphagia and regurgitation. The acute history of excessive vomiting is more suggestive of oesophageal rupture, achalasia would likely present with a longer history. Hiatus hernia The cardia protrudes into the thoracic cavity through the phrenoesophageal membrane into the thoracic cavity in a hiatus hernia. The most common is a sliding hiatus hernia, which causes symptoms of reflux. It is unlikely to present with a patient in extremis. Mallory–Weiss tear A Mallory–Weiss tear is a tear in the mucosal lining of the oesophagus that classically occurs after heavily vomiting (often following an alcohol binge as described in the case history). Given the patient is in extremis, this is not likely to be the cause as most cases of bleeding from this are self-limiting and usually minor. Oesophageal cancer Oesophageal cancer in a young patient would be rare.

Answer 24

Explanation Mallory–Weiss tear A Mallory–Weiss tear occurs after excessive vomiting, often secondary to alcohol and involves a mucosal tear in the mucosa and submucosa. In most cases the bleeding is minor and self-limiting, and no intervention is required. Achalasia Achalasia refers to oesophageal dysmotility secondary to failure of smooth muscle of the lower oesophageal sphincter to relax during swallowing. It causes progressive dysphagia and regurgitation. The acute history of excessive vomiting and alcohol binge is more suggestive of a Mallory–Weiss tear, achalasia would likely present with a longer history. Diffuse oesophageal spasm This is a disorder of oesophageal dysmotility causing uncoordinated contractions of the oesophagus. Diagnosis can be difficult but it usually presents with intermittent non- cardiac retrosternal pain and dysphagia. Para-oesophageal hernia The acute history given would not support the diagnosis of a para-oesophageal hernia as this tends to present with reflux symptoms and dysphagia. Oesophageal Ca This would present with weight loss and dysphagia for which the patient has no history. Additionally, oesophageal cancer in a 24-year-old would be rare.

Answer 25

Explanation Gallstone ileus It is unusual for a gallstone to cause problems outside of the biliary tree, but sometimes a gallstone can pass into the small bowel and cause an obstruction known as a gallstone ileus. This occurs after formation of a cholecystoduodenal fistula between the gall-bladder and duodenum. This causes the presence of air in the biliary tree, (ie pneumobilia), which can be seen on imaging. Caecal volvulus A caecal volvulus would cause dilated loops of small bowel, however, it would not cause pneumobilia, which is presence of air in the biliary tree, and is more indicative of gallstone ileus. Crohn’s disease Crohn’s disease is an inflammatory bowel disease and can affect the entire length of the gastrointestinal tract with transmural inflammation noted and although Crohn’s disease can cause obstruction, pneumobilia is unlikely. Additionally, the history is more indicative of cholecystitis secondary to gallstones. Diverticular stricture The lack of air in the rectum suggests an obstructive picture and the absence of dilated large bowel loops goes against the diagnosis of large bowel obstruction caused by a diverticular stricture. Sigmoid volvulus A sigmoid volvulus causes a classic coffee-bean sign on abdominal X-ray.

Answer 26

Explanation All of the above The possibilities of presentation of appendicitis are numerous; good knowledge of the signs and symptoms of appendicitis is paramount as it is often a clinical diagnosis, supported with evidence of inflammation in the blood results, and occasionally with imaging, primarily ultrasound or in older patients computed tomography (CT) scan. Colicky central abdominal pain shifting to right iliac fossa The usual presenting history is of colicky and vague central abdominal pain shifting to the right iliac fossa after 24 h and becoming constant with associated nausea and pyrexia. Dysuria, frequency of micturition and fever History may mimic urinary tract infection with dysuria, frequency and fever. This generally occurs when the appendix lies on or adjacent to the bladder. Nausea and vomiting Nausea and vomiting are common associated symptoms of appendicitis, and are usually seen as the condition progresses. Sharp localised pain, worse on movement and found at McBurney's point The classical area of maximal tenderness is one-third of the distance from the anterior superior iliac spine (ASIS) to the umbilicus. This is McBurney’s point. Specific signs on abdominal examination are as follows:  Psoas stretch sign – passive extension or hyperextension of the hip increases abdominal pain due to the psoas muscle being in contact with the inflamed appendix.  Rovsing’s sign – Palpation in the left iliac fossa may produce pain at the site of tenderness in the right iliac fossa due to movement of the inflamed parietal peritoneum.

Answer 27

Explanation Gastric volvulus Gastric volvulus classically involves Borchardt’s triad; epigastric pain, retching without vomiting and the inability to pass an NG tube. The twisting can occur in two ways: along the long axis of the stomach (organoaxial) or around the axis perpendicular to the stomach (mesenteroaxial). Oesophageal perforation Oesophageal rupture or perforation occurs mostly either secondary to trauma eg during endoscopy or due to prolonged forceful vomiting. It is likely to also cause retrosternal pain and would not prevent passage of an NG tube. Perforated duodenal ulcer A perforated ulcer will cause epigastric abdominal pain with peritonitis and possibly guarding depending on the extent of the perforation. Additionally, it would not obstruct the passage of a nasogastric tube. Sigmoid volvulus Sigmoid volvulus is more likely to present with abdominal pain and complete constipation. If vomiting were to occur, it would be faeculent in nature. Small bowel obstruction This would not prevent the passage of an NG tube.

Answer 28

Explanation Urgently call the paediatric anaesthetist The child has acute epiglottitis. Acute epiglottitis tends to present with a rapidly progressive sore throat and in the late stages, may be associated with inspiratory stridor. The child will be toxic with a raised temperature and tends to sit forwards and drool. The loose connective tissue swelling in the epiglottis can occlude the airway and care must be taken to avoid this. Any attempts to examine the child, including simple cannulation can precipitate laryngospasm and airway occlusion. Therefore the most important step in managing this patient is to get the help of someone with experience in managing paediatric airways. Examination of the oropharynx Any attempts to examine the child, including examination of the oropharynx can precipitate laryngospasm and airway occlusion, and therefore is ill advised and should be avoided. Flexible laryngoscopy As mentioned, any attempt to examine this child may trigger life-threatening airway occlusion and so should be avoided. IV access and blood cultures While this child is likely to be septic given the history, no attempt to cannulate the patient should be undertaken as this may cause airway obstruction. IV antibiotics This would require cannulation, which should not be undertaken.

Answer 29

Explanation Use of silver nitrate Application of sustained pressure for epistaxis is the primary first aid measure. If unsuccessful, silver nitrate or chemical cautery can be utilised and can be very effective in stemming epistaxis. However, in higher risk patients (particularly the elderly on anticoagulation), nasal packing, both anterior and posterior, may be required. Progression to surgery and artery ligation would then be the next management method. Embolisation Maxillary artery embolisation is becoming a more frequently used alternative to artery ligation, however, this is reserved for specialist interventional radiology centres, and would only be indicated for refractory bleeding despite cautery and nasal packing. External carotid artery ligation Ligation of the external carotid artery is reserved for life-threatening epistaxis, other measures should be trialled to stem bleeding before artery ligation. Sphenopalatine artery ligation Ligation of local arteries, such as the sphenopalatine, may be required and are not uncommon, however, more conservative measures should be trialled before progression to surgical ligation. Trans-sphenoidal ligation This is not indicated for epistaxis.

Answer 30

Explanation Amoebic liver abscess Amoebic liver abscesses often occur secondary to Entamoeba histolytica infection in the gut entering the portal circulation and spreading to the liver. The condition occurs mostly in endemic areas and affects travellers visiting them. Clinical features include abdominal pain (most commonly in the right upper quadrant), fever, rigours and nausea/vomiting. Some patients will report a history of dysentery recently. Imaging with ultrasound scan or computed tomography (CT) is useful in the diagnosis, and can be combined with aspiration which produces a thick fluid resembling anchovy sauce. Treatment mostly consists of metronidazole sometimes with percutaneous drainage. Cholangiocarcinoma Cholangiocarcinoma would be rare in an 18-year-old adult. Gallstones Gallstones presents with colicky, right upper quadrant abdominal pain. It may be associated with pyrexia if there is cholecystitis. It would be uncommon in young men, more often presenting in overweight, middle-aged women. As such, the case history does not fit with this diagnosis. Hydatid disease Hydatid disease is caused by parasitic Echinococcus tapeworms, it causes the formation of slow growing cysts, usually in the liver or lungs, containing hydatid fluid. Patients can often be asymptomatic. Intermediate hosts are grazing animals, with dog and cats often acting as definitive hosts. Humans are only accidental hosts. Given this patient has a history of dysentery while travelling, this supports the diagnosis of amoebic abscess formation, as opposed to hydatid disease. Pancreatitis This commonly presents with epigastric abdominal pain radiating through to the back. The most common aetiology in the UK are gallstones or alcohol, both of which would be unlikely in a young adult.

Answer 31

Explanation Cholecystitis Acalculous cholecystitis is rare, but can occur in critically ill patients often on the intensive care unit. The mechanism for this is thought to involve gall- bladder stasis due to analgesia or parenteral nutrition. Imaging includes ultrasound, which can show a dilated gall-bladder with oedema in the wall. Aorta-enteric fistulae Aortic-enteric fistulae occur mostly following abdominal aortic aneurysm (AAA) repair in which a communication has developed between the aorta and the small bowel. They result in very heavy blood loss into the small bowel and are often fatal. Biliary colic Biliary colic secondary to gallstones is common and presents as colicky abdominal pain. Given that no gallstones were identified on ultrasound and the prolonged stay in intensive care, this is less likely than acalculous cholecystitis. Ileus Ileus is common in patients who have undergone major abdominal surgery and is often due to handling of the bowel during the operation. It usually resolves after a few days and ‘bowel rest’. The findings of a distended gall-bladder suggest a more likely pathology. Pancreatitis Pancreatitis usually presents with epigastric pain, and the most common causes are gallstones or alcohol. Given no gallstones were identified on ultrasound but the gall- bladderis distended and oedematous, acalculous cholecystitis must be considered. Moreover, this patient has normal lipase and amylase levels.

Answer 32

Explanation Severe The modified Glasgow criteria can be used to assess the severity of acute pancreatitis by using parameters taken within the first 48 h following admission. The most common aetiologies in the UK are either gallstones or alcohol. This patient has significantly deranged physiological and biochemical markers, increasing their Glasgow score, indicating a severe pancreatitis. Mild = 1 positive factor, moderate = 2 factors, severe = 3 positive factor. Mild The patient has significant derangements of the physiological and biochemical markers used to assess severity of pancreatitis, increasing the Glasgow score above the mild category. Moderate As above, the patient has significant derangements in the parameters used to calculate the Glasgow score, causing the severity to be categorised as severe. Haemorrhagic The terms haemorrhagic and necrotic describe the computed tomography (CT) scan appearance of the pancreas, and influence the Balthazar score. Necrotic Again, this term is reserved for describing the appearance of the pancreas on CT.

Answer 33

Explanation Glasgow The modified Glasgow criteria can be used to assess the severity of acute pancreatitis by using parameters taken within the first 48 h following admission. APACHE The APACHE score requires additional information to those provided eg blood pressure, urine output and is used to assess mortality risk for patients admitted to intensive care regardless of causative pathology. Balthazar The Balthazar grade is based on the computed tomography (CT) scan appearance of the pancreas. Hinchey The Hinchey classification grades diverticulitis not pancreatitis. Ranson Ranson’s criteria are valid for alcohol-induced pancreatitis and can only be applied after 48 h. The severity of acute pancreatitis is typically classified based on various criteria, including clinical, biochemical, and radiological parameters. Here are some commonly used criteria: 1. Ranson’s Criteria: Developed by Dr. John Ranson in the 1970s, this system includes 11 criteria—5 assessed at admission and 6 during the first 48 hours. The presence of 3 or more of these criteria indicates severe pancreatitis and a poorer prognosis. 2. APACHE II Score (Acute Physiology and Chronic Health Evaluation II): This scoring system evaluates physiological parameters within the first 24 hours of admission. A higher score indicates a more severe condition and a worse prognosis. 3. Balthazar Score: This system assesses the severity of pancreatitis based on CT imaging findings. It uses a grading system from A to E, with E indicating the most severe form of pancreatitis. 4. Imrie Score: Similar to Ranson’s criteria, the Imrie scoring system evaluates clinical and laboratory parameters to predict the severity of pancreatitis. A score of 3 or more indicates severe pancreatitis. 5. CT Severity Index (CTSI): This index evaluates the extent of pancreatic and peripancreatic inflammation on CT imaging. It helps in predicting the severity of pancreatitis and guiding management decisions. 6. Bedside Index for Severity in Acute Pancreatitis (BISAP): This simplified scoring system assesses five parameters at admission—blood urea nitrogen, impaired mental status, systemic inflammatory response syndrome, age, and pleural effusion—to predict the severity of acute pancreatitis. 7. CRP (C-reactive protein): Elevated levels of CRP have been associated with severe acute pancreatitis and can be used as a marker for assessing severity. 8. Modified Glasgow Criteria: Similar to Glasgow Coma Scale, this criteria assesses various clinical parameters and organ dysfunction to predict the severity of pancreatitis. These criteria help clinicians in assessing the severity of acute pancreatitis, guiding treatment decisions, and predicting patient outcomes. Sources: • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734411/ • https://www.ncbi.nlm.nih.gov/books/NBK482291/

Answer 34

Explanation Emergency laparotomy This patient has a small bowel obstruction secondary to gallstone ileus. This is a surgical emergency requiring urgent laparotomy. The gallstone usually impacts proximal to the ileocaecal valve, and so it should be massaged through into the large intestine or extracted via an enterotomy, so relieving the obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) This intervention is used for the diagnosis and treatment of gallstones located in the common bile duct. Again, this will not solve the small bowel obstruction which requires emergency intervention. Laparoscopic cholecystectomy Laparoscopic cholecystectomy is indicated for those with recurrent cholecystitis with evidence of gallstones. This does not, however, address the small bowel obstruction which is a surgical emergency requiring laparotomy. Percutaneous drainage of the gall bladder Small bowel obstruction is a surgical emergency and requires intervention. Percutaneous drainage of the gall bladder will not resolve the bowel obstruction and therefore would be inappropriate. Surgical closure of a cholecystoduodenal fistula The gallstone will have passed into the small bowel through a biliary-enteric fistula, but this does not usually require surgical repair. Such fistulae often lead to pneumobilia, which can be seen on plain abdominal radiographs.

Answer 35

Explanation Courvoisier’s law Courvoisier’s law states that in the event of painless jaundice and a palpable gall bladder, the cause is unlikely to be gallstones. This is because the presence of gallstones tends to make the gall bladder fibrosed, and therefore it is unlikely to become distended in the event of an obstruction of the biliary tree. Cope sign Cope sign involves flexion and internal rotation of the right hip, causing pain if the appendix is lying in close relation to the obturator internus. Murphy’s sign Murphy’s sign occurs when, upon pressing over the RUQ with two fingers, asking the patient to breathe in causes pain and arrest of inspiration, as the inflamed gall bladder impinges on the examiner’s fingers. Psoas sign Psoas sign involves extension of the hip, causing pain if there is a retrocaecal appendix. Rovsing’s sign Rovsing’s sign describes pain in the right iliac fossa more than in the left iliac fossa when the left iliac fossa is pressed.

Answer 36

Explanation Budd–Chiari syndrome Portal hypertension with a pressure of over 20 mmHg is commonly caused by pre-hepatic problems such as portal vein thrombosis, hepatic disease such as cirrhosis and post-hepatic problems such as tricuspid valve incompetence and Budd–Chiari syndrome of hepatic vein thrombosis. Budd–Chiari syndrome commonly results in hepatosplenomegaly and ascites. It is associated with pregnancy and being postpartum. Use of the oral contraceptive pill can also increase the risk for venous thromboembolic disease. Alcoholic cirrhosis There is no history of alcohol excess in the history given, so alcoholic cirrhosis would be unlikely. Pylephlebitis after acute appendicitis Pylephlebitis is an uncommon thrombophlebitis of the portal vein, caused by an infection such as appendicitis. The case history given, however, is not consistent with appendicitis, which commonly presents with vague, centralised abdominal pain, localising to the right iliac fossa over 24 hours. Splenectomy Palpable splenomegaly is noted on examination; therefore, splenectomy cannot be the cause. Tricuspid valve incompetence Although tricuspid valve incompetence can cause portal hypertension, and subsequently hepatosplenomegaly, as described in the case history, as the patient is postpartum, Budd–Chiari syndrome is the more likely diagnosis.

Answer 37

Explanation Computerised tomographic scan of the abdomen and pelvis For this scenario, the differential diagnosis is pseudo-obstruction, sigmoid volvulus and carcinoma of the distal colon/rectum. Computerised tomography of the abdomen and pelvis is the best option, as it permits the diagnosis to be obtained and the correct treatment instituted. Pseudo-obstruction may be associated with an underlying precipitating condition such as renal failure, electrolyte abnormalities, myxoedema, stroke, myocardial infarction, chest infection and retroperitoneal malignancy (pseudo- obstruction in the presence of retroperitoneal malignancy is known as Ogilvie syndrome). Medical management comprises correction of electrolyte abnormalities, treatment of the underlying cause and use of the anticholinergic neostigmine (with heart monitor surveillance). Laparotomy and sigmoid colectomy At present, the diagnosis is not clear and further imaging is required, so the most appropriate treatment can be initiated. Sigmoid colectomy is indicated in an elective setting for recurrent sigmoid volvulus. Sigmoid volvulus often has the characteristic ‘coffee bean’ sign on plain abdominal radiograph. Obstructed colon caused by a distal neoplasm is open to several surgical options following adequate resuscitation. These include stenting, defunctioning stoma, primary resection and anastomosis following on- table colonic lavage or Hartmann’s procedure. Note if the patient was too unstable for the computerised tomography scanner, then exploratory laparotomy may indeed be indicated first. Laxatives Initiating treatment before identifying the causative pathology could cause further harm to the patient. For example, if the obstruction is caused by a carcinoma of the sigmoid colon, use of laxatives could precipitate a perforation. Sigmoidoscopy Sigmoidoscopy may be beneficial in decompressing the colon with a flatus tube when a sigmoid volvulus is the causative pathology. However, the diagnosis is not clear in this case, so further imaging is required before intervention. Fixation procedures for recurrent sigmoid volvulus, such as sigmoidopexy, have been performed but are associated with high recurrence rates. Trephine ileostomy This is an operative technique to create a permanent end-colostomy without undergoing a laparotomy. Again, this would not be indicated until the diagnosis is clarified with further imaging.

Answer 38

Explanation Adhesional small bowel obstruction This patient has a number of characteristic features of small bowel obstruction: vomiting, constipation and abdominal distension. Adhesions are the most common cause of small bowel obstruction in the developed world and can occur following any form of abdominal surgery. Aorto-enteric fistula Aortic-enteric fistulae occur mostly following AAA repair, in which a communication has developed between the aorta and the small bowel. They result in very heavy blood loss into the small bowel, causing rectal bleeding, and are often fatal. Incisional hernia There is nothing in the history of the case to suggest the patient has an incisional hernia which could be causing obstruction. Diverticular disease There are no features in the case history that suggest diverticular disease as the cause for obstruction. Sigmoid tumour Carcinoma of the colon, particularly the sigmoid colon, is a common cause for large bowel obstruction. However, there are no features in the history that point to a sigmoid tumour as the cause for obstruction, and given this gentleman has had previous major abdominal surgery, adhesional bowel obstruction is more likely.

Answer 39

Explanation Insertion of flatus tube The coffee bean sign and clinical history are highly suggestive of sigmoid volvulus, which commonly occurs in elderly patients who have a chronic history of constipation. Insertion of a flatus tube represents a relatively low-risk procedure that could potentially resolve the patient’s symptoms and therefore would be a good first-line option. If this fails, the next step would be flexible sigmoidoscopy. Antibiotics Antibiotics are not indicated, as there are no features in the case history suggestive of infection. Computerised tomography (CT) scan A CT scan would confirm the diagnosis but offers no therapeutic benefit to the patient. Exploratory laparotomy Given the patient’s pre-morbid status of being a bed-bound nursing home patient, the risks of any major surgery, eg laparotomy, would be great. Depending on the severity of the patient’s dementia, they may also lack capacity to consent to surgery, and it is likely to be against the patient’s best interests to undergo major surgery. Sigmoid colectomy Again, major surgery for this patient would be ill-advised.

Answer 40

Explanation Pseudo-obstruction The history of vomiting, constipation and a distended abdomen is suggestive of an obstruction. In this case, this gentleman has developed pseudo-obstruction, which often resembles bowel obstruction and can occur in any post-operative patients and can also be triggered by deranged electrolytes, eg hypokalaemia. It is best managed conservatively through correcting the underlying causes. Adhesional small bowel obstruction The most common cause for small bowel obstruction, namely adhesions, is unlikely in this case, given the patient has never had abdominal surgery. Constipation secondary to opioids Although the patient is likely to have been prescribed opioid-based medication before and following the hemi-arthroplasty, his empty rectum points away from constipation. Incisional hernia No hernias are palpable on examination and he has not previously undergone abdominal surgery; as such, this is incorrect. Obstruction hernia This is unlikely, as there are no palpable hernias on examination and no history of previous abdominal surgery.

Answer 41

Explanation Obturator hernia Pain which radiates to the thigh is suggestive of pressure on the obturator nerve which supplies sensation to the medial thigh. This can be present in around 50% of patients with an obturator hernia. Obturator hernias occur most commonly in frail old women and often there are no signs. If pressure is present over the obturator nerve, patients often hold the leg flexed to reduce pain. Rectal, and more often vaginal, examination can reveal a swelling in the region of the obturator foramen. Adhesional small bowel obstruction Although the most common cause of small bowel obstruction is adhesions in the developed world, the lack of previous surgery makes this very unlikely. Epigastric hernia An epigastric hernia would not cause pain in the medial thigh and vaginal examination would be unremarkable. Furthermore, an epigastric hernia was not identified on examination of the abdomen. Para-umbilical hernia There were no hernias identified on abdominal examination, and a lack of previous abdominal surgery makes this diagnosis unlikely. Sigmoid volvulus Sigmoid volvulus is a common cause for bowel obstruction, particularly in the elderly. However, it would not produce pain in the medial thigh and vaginal examination would be unremarkable.

Answer 42

Explanation Compartment syndrome Compartment syndrome is characterised by increased pressure within an unyielding osseofascial compartment, resulting in local tissue hypoxia. The earliest sign is pain out of proportion with the injury, particularly severe pain on passive muscle stretch. Pallor, paraesthesiae and pulselessness occur in late stages. Diagnosis is on clinical grounds, although compartment pressures can be measured. Raised creatine kinase (CK) levels are indicative of muscle necrosis. Fasciotomies to release the deep and superficial compartments should be performed early. Although more common in the lower limb, it is possible in the upper limb as well. Deep vein thrombosis While venous thromboembolic disease should be considered in those with prolonged immobilisation of a limb, development of a deep vein thrombosis within 8 hours is improbable. Early infection Infection of the limb may be painful. However, there are no other signs of infection in the case history. Moreover, compartment syndrome should always be considered in an acutely painful limb which has recently been immobilised in a plaster cast. Inadequate analgesia Adequate analgesia is important. However, effective immobilisation should provide sufficient pain relief. The history described is highly suggestive of compartment syndrome. Necrotising fascitis Necrotising fasciitis is a surgical emergency caused by bacterial infection of the fascia and subsequent necrosis of the subcutaneous tissues. It requires emergency debridement of affected areas with wide margins and intravenous antibiotics. In the case history, there is no suggestion of sepsis with haemodynamic compromise, which would be seen with necrotising fasciitis.

Answer 43

Explanation Toxic shock syndrome An unwell child with an unhealed burn must be treated for toxic shock syndrome until proven otherwise. Treatment will require management in the Intensive Care Department, with input from a paediatric consultant and the plastic surgery team. Circulatory support with cryoprecipitate may be necessary. Anaphylaxis This is a paediatric airway emergency which requires emergency administration of intramuscular adrenaline to prevent airway occlusion from a hypersensitivity reaction. The history described is not consistent with anaphylaxis, which presents rapidly with lip and tongue swelling, airway compromise and difficulty breathing. Haemophilus influenzae There is no suggestion of respiratory signs or symptoms in the case history, so this is unlikely, despite being a common paediatric presentation. Meningococcal septicaemia Meningococcal meningitis leading to septicaemia is life-threatening and should always be considered in an acutely unwell child. However, given the unhealed burn, toxic shock syndrome is more probable. Salmonella Salmonella infection would present with gastrointestinal symptoms and signs, of which there are none in the case history, other than anorexia which is a common and non- specific symptom for an unwell child.

Answer 44

Explanation Meckel’s diverticulum The description of an outpouching in this location on the antimesenteric border is consistent with a Meckel’s diverticulum. These are embryological remnants of the vitello-intestinal duct and are a free diverticulum of the terminal ileum. They occur in 2% of the population, are commonly 2 feet (60 cm) from the ileocaecal valve, often 2 inches (5 cm) in length and twice as common in men than women. Acute inflammation may mimic appendicitis and it is important when performing an appendicectomy to search for a Meckel’s diverticulum if the appendix is normal. Abdominal tuberculosis (TB) The case history is not consistent with abdominal TB and no risk factor for TB is described. Appendicitis The normal appendix goes against a diagnosis of acute appendicitis. Caecal carcinoma The normal caecum makes a caecal tumour causes the symptoms very unlikely, furthermore, a caecal carcinoma in a 17-year-old adolescent would be rare. Crohn’s disease The lack of inflammation in the terminal ileum makes Crohn’s unlikely.

Answer 45

Explanation Intravenous antibiotics and close monitoring This elderly patient has a localised diverticular perforation with absence of peritonitis and is showing signs of improvement. She has significant past medical history that would make her a high risk candidate for surgery, therefore conservative management with IV antibiotics and close monitoring for signs of deterioration is the best management path. Discharge Discharge is obviously not appropriate at this point. Laparotomy and primary anastomosis A primary anastomosis would not be advisable in an acute case with potential contamination leading to a higher chance of anastomotic leak. An anastomotic leak could be disastrous in this patient and so a colostomy would be best surgical practice if she were to be taken to theatre. Laparoscopic resection If surgical intervention were required, laparoscopy may be difficult due to her COPD, particularly as carbon dioxide insufflation of the abdominal cavity will splint the diaphragm, making ventilation more difficult. Laxatives Laxatives are not the primary concern in this patient’s acute management.

Answer 46

Explanation Pseudomembranous colitis The appearance of pseudomembranes are typical for pseudomembranous colitis caused by Clostridium difficile. This pathogen is more common in nursing home or hospitalised patients, and is often associated with antibiotic use. High risk antibiotics include; fluoroquinolones, cephalosporins and clindamycin. Prevention of the spread of C. difficileinvolves isolation of infected patients, judicious hand hygiene and measured antibiotic use. Crohn’s disease Crohn’s disease is an inflammatory bowel condition affecting the entire length of the gastrointestinal tract. Biopsy would demonstrate transmural inflammation and presentation of Crohn’s disease is usually in early 20s. Melanosis Coli This is a benign condition identified on colonoscopy in which there is a disorder of pigmentation of the endothelium of the colon. As the condition is benign, it would not produce the symptoms described in the case history. Malignancy Malignancy can present with a change in bowel habit, although it is usually less dramatic than severe diarrhoea, while malignancies are usually painless until complications such as perforation or obstruction occur. Ulcerative Colitis Ulcerative colitis is an inflammatory bowel disease in which inflammation is limited to the colon. It presents in the early 20s, so a diagnosis of ulcerative colitis in the elderly is uncommon.

Answer 47

Explanation Flexor tendon sheath infection A flexor tendon sheath infection is an infection of the sheath that forms the lubricating surface around the flexor tendons to the hand. This constitutes an emergency as severe infection can destroy these surfaces resulting in a painful and stiff finger. In most cases there will be a history of penetrating trauma before the infection. There are four main signs of a flexor tendon sheath infection: *diffuse swelling of the digit *the digit will be partially flexed *tenderness along the flexor tendon sheath *pain on passive extension of the digit. Cellulitis Cellulitis would certainly be included in the differential diagnosis given the case history, however, cellulitis would not cause severe pain on passive extension of the finger. Foreign body This will likely produce localised inflammation and swelling around the site of the foreign body. Additionally, pain on passively extending the finger suggests tendon sheath infection. Mallet finger Mallet finger describes the deformity of disruption of the extensor digitorum tendon at the distal interphalangeal joint with blunt force trauma being the causative injury. The deformity is not described and the patient has not suffered blunt force trauma in the case history. Paronychia Paronychia is a local infection around a fingernail that often begins as a cellulitis before developing into an abscess which requires drainage. This is not described in the case history above.

Answer 48

Correct Answer: 5. Urinary obstruction, infection, reduced blood supply and drug toxicity should be considered before treating for acute graft rejection Explanation: In the immediate post-transplant period, a rise in serum creatinine accompanied by fever and oliguria can be due to several potential causes. While acute rejection is a possibility, it is crucial to first rule out other common causes such as: • Urinary obstruction: Check for any blockages in the urinary tract. • Infection: Infections can cause fever and impact kidney function, and must be treated appropriately. • Reduced blood supply: Ensure that the transplanted kidney is receiving adequate blood flow. • Drug toxicity: Medications used post-transplant can sometimes be nephrotoxic. It is important to conduct a thorough evaluation to rule out these causes before initiating treatment for acute graft rejection. This approach helps to avoid unnecessary immunosuppressive therapy and addresses any reversible causes of graft dysfunction. Therefore, the correct management strategy in this scenario is to consider and investigate other potential causes of the symptoms before treating for acute graft rejection.

Answer 49

Correct Answer: 4. Necrotising fasciitis Explanation: Necrotising fasciitis is a severe, rapidly progressing soft tissue infection characterized by widespread necrosis of the fascia and subcutaneous tissue. The key features in this case that point towards necrotising fasciitis include: • Rapid progression of infection: The infection is advancing rapidly along the fascial planes. • Severe systemic signs: The patient has metabolic acidosis, declining blood pressure, and urine output, indicating severe sepsis or septic shock. • Characteristic skin changes: The reddish-bronze discoloration and decreased sensation are typical signs of necrotising fasciitis. • Tenderness and pain: Severe pain and tenderness beyond what is expected for cellulitis. These findings distinguish necrotising fasciitis from other conditions such as cellulitis, compartment syndrome, myositis, and rhabdomyolysis, which do not typically present with such rapid progression and systemic deterioration. Immediate surgical intervention and broad-spectrum antibiotics are critical in the management of necrotising fasciitis to prevent further tissue destruction and systemic complications. Explanation Necrotising fasciitis The progressive symptoms and signs with progressive haemodynamic compromise is highly suggestive of necrotising fasciitis. It is a surgical emergency requiring debridement with wide margins and treatment with high dose intravenous antibiotics. Necrotising fasciitis often involves an initial focus such as a puncture wound, insect bite, or scratch, and usually begins like cellulitis with hot, red and tender skin. However, there may be an initial dissemination in the deeper tissue planes in the absence of surface changes. At the leading edge of infection, there is reddish or bronze discoloration of the skin and decreased sensation. The margin of infection advances rapidly along fascial planes with thrombosis of perforating vessels, oedema, necrosis and sloughing of the skin occur. Haemorrhagic bullae are relatively common. Clinical features can be divided into early findings, which include pain, cellulitis, pyrexia, tachycardia, swelling, induration and skin anaesthesia. Late findings may include severe pain, purple or black skin discoloration, blistering, haemorrhagic bullae, crepitus, discharge of ‘dishwater’ fluid, severe sepsis or systemic inflammatory response syndrome and multiorgan failure. Cellulitis The condition has progressed from a simple cellulitis to necrotising fasciitis given the worsening condition of the patient and clinical signs of a rapidly spreading fascial infection. Compartment syndrome Compartment syndrome is characterised by increased pressure within an unyielding osseofascial compartment, resulting in local tissue hypoxia. It is often an early complication of long bone fractures. The case history given is not consistent with compartment syndrome. Myositis Myositis is a broad term used to describe inflammation of the muscles, of which there can be many causes including infection, medications, trauma or be immune mediated. It would not be associated with rapidly advancing skin changes or significant haemodynamic compromise. Rhabdomyolysis This is condition causing skeletal muscle to break down rapidly following either direct or indirect injury, and is a common pathology following a crush injury. A rapid accumulation of myoglobin can cause significant renal failure. Again, rhabdomyolysis would not produce skin changes and the history is consistent with necrotising fasciitis.

Answer 50

Correct Answer: 3. Meningococcal sepsis Explanation: The patient’s presentation is highly suggestive of meningococcal sepsis, which is a life-threatening condition caused by the bacterium Neisseria meningitidis. The key features pointing towards this diagnosis include: • Altered behaviour and reduced consciousness: Suggest central nervous system involvement. • Fever and sore throat: Common initial symptoms of an infection. • Rash: The rash described, which spreads from the torso to the limbs, is characteristic of the petechial or purpuric rash seen in meningococcal sepsis. • Neck stiffness: A sign of meningitis, which often accompanies meningococcal infection. Other Options: 1. Disseminating intravascular coagulopathy (DIC): A serious condition that involves widespread blood clotting and bleeding, but it does not typically present with the combination of symptoms described. 2. HIV seroconversion: Can present with fever and rash, but the acute presentation of reduced consciousness and neck stiffness is not typical. 3. Staphylococcus scalded skin syndrome: Characterized by widespread redness and skin peeling, typically without the severe systemic symptoms described. 4. Viral infection: While it can present with fever and rash, the severity of symptoms and rapid progression is more indicative of a bacterial cause such as meningococcal sepsis. Given the critical nature of meningococcal sepsis and the need for urgent treatment, this is the most likely diagnosis.

Answer 51

Correct Answer: 2. C. difficile Explanation: The patient’s presentation is highly suggestive of a Clostridium difficile (C. difficile) infection, which is a common cause of antibiotic-associated colitis. The key features include: • Recent antibiotic use: She was recently treated for pneumonia, likely with antibiotics, which is a major risk factor for developing C. difficile infection. • Bloody diarrhea and abdominal cramps: These are classic symptoms of C. difficile colitis. • Fever and leucocytosis: Indicate an infectious process, commonly seen in severe C. difficile infection. Other Options: 1. Bowel cancer: While it can cause changes in bowel habits and bleeding, the acute presentation with fever and leukocytosis is more indicative of an infectious cause. 2. Campylobacter jejuni: Typically causes gastroenteritis with diarrhea, but the association with recent antibiotic use makes C. difficile more likely. 3. Inflammatory bowel disease (IBD): Can present with bloody diarrhea and abdominal pain, but the acute onset after antibiotic use and presence of fever and leukocytosis point more towards an infectious etiology. 4. Peptic ulcer: Usually presents with upper abdominal pain and possibly bleeding, but not with bloody diarrhea and systemic symptoms like fever and leukocytosis. Given the patient’s history of recent hospitalization and antibiotic treatment, C. difficile infection is the most likely diagnosis.

Answer 52

Correct Answer: 3. Psoas abscess Explanation: While renal calculi can present with many of these symptoms, the correct diagnosis in this context is a psoas abscess. The key features supporting this diagnosis include: • Constant right groin pain and limping: The psoas muscle, located in the retroperitoneal space, can cause referred pain to the groin and hip, leading to limping. • Nausea: Can occur due to systemic infection and inflammation. • Tenderness in the right groin: Psoas abscess often presents with pain that can be elicited on palpation or during movements that stretch the psoas muscle, such as hip flexion. • Raised white cells: Indicative of an infection. • Positive urine dipstick for blood: Can occur due to adjacent structures being affected or due to irritation/inflammation from the abscess. Other Options: 1. Cystitis: Typically presents with urinary symptoms like dysuria, frequency, and urgency, which are not highlighted in this case. 2. Incarcerated femoral hernia: Would likely present with a palpable mass and more acute, localized symptoms. 3. Pyelonephritis: Usually presents with systemic symptoms like fever, flank pain, and dysuria, and less commonly with significant groin pain and limping. 4. Renal calculi: Although possible, the presence of limping and the specific description of the groin pain suggests a muscular or soft tissue source, such as a psoas abscess. Given the clinical presentation, a psoas abscess is the most appropriate diagnosis.

Answer 53

Explanation Clostridium perfringens Gas gangrene can cause myonecrosis, gas production, and sepsis. It may progress to toxic shock rapidly. Features are large, blackened sores and crepitus caused by gas escaping the necrotic tissue. Clostridia are saprophytes; they live in soil and require a spore to protect them from dehydration. Clostridium perfringens, formerly C. welchii, can cause gas gangrene. There is gas production due to the proteolytic enzymes released by the organism. It also causes food poisoning at about 12–18 h after ingestion. This is caused by exotoxin production. Staphylococcus aureus Staphylococcus aureus is the commonest causative pathogen for cellulitis, however the case does not describe a simple cellulitis and another cause should be sought. Clostridium botulinum Also a member of the Clostridium genus, C. botulinum produces the exotoxin botulinum,which causes a flaccid paralysis as opposed to gas gangrene. Staphylococcus haemolyticus This bacteria is part of normal commensal skin flora, and is often the causative organism in opportunistic infections following a breach in the natural barrier of the skin, such as following cannulation. Pseudomonas aeruginosa Pseudomonas is an important pathogen with regard to hospital-acquired infections, multi-drug resistance and infections in immunocompromised patients. Diabetic patients with lower limb ulcers can often become colonised with Pseudomonas causing chronic non-healing ulcers, which are troublesome to treat. It does not however produce gas gangrene.

Answer 54

Explanation Felon A felon is an abscess in the compartments of the pulp. This is usually more painful than a paronychia. The swelling does not extend proximal to the distal interphalangeal joint. The infection often follows a penetrating trauma and is most common in the thumb and index finger. Apical infection An apical infection involves the apical space, ie between the distal part of the nail and the bone of the distal phalanx, infections of this space may occur when a splinter runs under the nail. Tenderness is greatest at or just under the free edge of the nail. Herpetic whitlow Herpetic whitlow is caused by the herpes simplex virus and small clear vesicles would be seen. Paronychia Paronychia is an infection beside or proximal to the nail, it usually begins as a simple cellulitis before progressing into a definite abscess which requires incision and drainage. Flexor tendon sheath infection Flexor tendon sheath infection is a surgical emergency with a sausage-shaped digit, flexed position, tenderness over the flexor tendon sheath and pain on passive extension.

Answer 55

Explanation Air enema The clinical picture is of intussusception which occurs in 0.4% of children. It is more common in boys, usually younger than 1 year old. Intussusception occurs when one section of the bowel invaginates into another, the most common form is ileocolic. Blood and mucus or ‘redcurrant jelly’ stool may be passed after the first 24 h as a late manifestation. Sausage-shaped mass may be felt in upper abdomen. Rectal examination is very important as occasionally the apex of intussusception is palpable. The majority of cases are successfully treated conservatively with an air enema. Emergency laparotomy Emergency operative management is only indicated in established peritonitis, perforation or failure of enema reduction. Lower gastrointestinal (GI) endoscopy Lower GI endoscopy would not be indicated given the clinical scenario, the initial management of choice would be an air enema. Rigid sigmoidoscopy Again, rigid sigmoidoscopy is not indicated. Stool softeners Stool softeners have no role in the treatment of intussusception.

Answer 56

Explanation Pulse rate The normal ranges for physiological variables and blood test results vary with age in children. The normal value for pulse rate in a infant aged between 1–2 is 100–120 beats per minute, therefore, this infant is tachycardic, which warrants further investigation. Haemoglobin The normal range for haemoglobin is 10.5–13.5 g/dl. Respiratory rate A normal respiratory rate for an infant aged 1–2 years old is 25–35. This will reduce with age. Urine output Normal urine output would be more than 1.5 ml/kg/h. White-cell count A normal white-cell count will range from 6–15 × 10 9 /l.

Answer 57

Explanation Cystic fibrosis The newborn has meconium ileus. Signs of this include a distended abdomen, bilious vomiting and an empty rectum. The commonest association is with cystic fibrosis, and 15% of children with cystic fibrosis have meconium ileus. Cerebral palsy Cerebral palsy is a broad diagnosis covering a number of neurodevelopmental conditions affecting movement and coordination. It is not associated with meconium ileus. Down syndrome Down syndrome is a genetic disorder resulting from trisomy of chromosome 21. It is associated with a number of conditions including congenital heart disease, epilepsy, hypothyroidism and leukaemia. Spina bifida This is a birth defect resulting in failure of closure of the meninges. While there may be bladder and bowel pathology due to failure of closure of the spinal cord, cystic fibrosis has the commonest associated with meconium ileus. Turner’s syndrome This is a genetic disorder seen in women in which there complete, or partial loss, of the X chromosome. It is not associated with meconium ileus.

Answer 58

Explanation Mesenteric adenitis Mesenteric adenitis is an inflammation of the mesenteric lymph node accompanied by a mild peritoneal reaction. It is most common between ages 5–10 years and often follows/accompanies an URTI. Acute appendicitis Acute appendicitis can be distinguished from mesenteric adenitis by lack of cervical lymphadenopathy, headache, mild abdominal pain, shifting tenderness and pyrexia greater than 38 °C. Constipation Constipation would not cause pyrexia or cervical lymphadenopathy. There are a number of causes of constipation in children including hypothyroidism, hypercalcaemia, and Hirschsprung’s disease. Crohn’s disease The incidence of Crohn’s disease in children is increasing, presentation is similar to adults, but children more commonly have extra-gastro-intestinal symptoms, none of which has been described in the case history. Meckel’s diverticulum Meckel’s diverticulum can present with similar symptoms to appendicitis, or with bleeding, perforation, intussusception, volvulus or obstruction.

Answer 59

The most likely diagnosis for this patient is: Intussusception Explanation: 1. Intussusception: This is a condition where a part of the intestine telescopes into an adjacent part, causing a blockage. It typically presents with intermittent abdominal pain, vomiting, bloody stools (often described as “currant jelly” stools), and a palpable sausage-shaped mass in the abdomen. The presence of blood on rectal examination supports this diagnosis. 2. Infantile Hypertrophic Pyloric Stenosis: This condition presents with projectile vomiting in infants but does not typically cause bloody stools or a palpable abdominal mass. 3. Duodenal Atresia: This congenital condition causes bilious vomiting in newborns and is usually diagnosed shortly after birth. It does not typically present with bloody stools or a palpable mass. 4. Meconium Ileus: Often associated with cystic fibrosis, this condition presents with bowel obstruction in newborns and meconium impaction but not with the acute symptoms described in this case. 5. Hirschsprung’s Disease: This condition involves a lack of nerve cells in parts of the colon, leading to severe constipation and abdominal distension. It does not typically present with acute episodes of crying, vomiting, or bloody stools. Given the clinical presentation, intussusception is the most likely diagnosis.

Answer 60

The most common cause of obstruction in the first 2 years of life is: Intussusception Explanation: 1. Intussusception: This is the most common cause of intestinal obstruction in young children, particularly between the ages of 6 months and 2 years. It occurs when a part of the intestine telescopes into an adjacent segment, leading to obstruction, reduced blood flow, and potentially severe complications. The classic presentation includes episodic crying, abdominal pain, vomiting, and the passage of “currant jelly” stools. A palpable sausage-shaped mass is a key clinical finding. 2. Hirschsprung’s Disease: While this condition can cause chronic constipation and abdominal distension due to a lack of ganglion cells in the colon, it is not the most common cause of acute intestinal obstruction in this age group. 3. Hyperthyroidism: This condition is rare in infants and does not typically present with acute intestinal obstruction. 4. Coeliac Disease: This autoimmune disorder affects the small intestine due to gluten sensitivity and can cause chronic symptoms such as diarrhea, malabsorption, and failure to thrive, but it is not typically associated with acute intestinal obstruction in infants. 5. Hypercalcaemia: Elevated calcium levels can lead to constipation but are not a common cause of intestinal obstruction in infants. Given the clinical presentation of a distended abdomen, absence of stool production, and a palpable sausage-shaped mass, intussusception is the most likely diagnosis.

Answer 61

Explanation Pancreatitis This patient is most likely to have pancreatitis possibly caused by thiazide diuretic use. However, the most common cause is alcohol and gallstones in the UK and evidence of this must be sought on history and ultrasound scan. A significantly raised amylase should be apparent on the blood results, >1000 U/l (normal <200 U/l) is virtually diagnostic but beware that peritonitis and perforated duodenal ulcer for example can give similar appearances and a raised. Some units now use serum lipase which can be more sensitive. Pancreatitis can lead to vomiting but the X-ray appearance alludes to a sentinel loop – a paralytic ileus of duodenal or jejunal small bowel caused by local inflammation of the pancreas. Aortic dissection Of course in this age group, ruptured abdominal aortic aneurysm (AAA) and aortic dissection must be a consideration and vitally ruled out. Look for evidence of a pulsatile epigastric mass and difference in blood pressure in both arms. Computed tomography (CT) aortogram is suggested if there is any doubt, to rule out these other diagnoses. Biliary Colic Biliary colic more commonly presents with intermittent, colicky pain in the right upper quadrant and does not radiate through to the back. Renal Colic In renal colic, patients usually cannot get comfortable due to the spasmodic nature of the pain and urine dip may show blood. Ruptured aortic aneurysm As above, this is an important diagnosis to exclude, however, the case history is more consistent with acute pancreatitis.

Answer 62

To diagnose septic shock according to the recent NICE guidelines, you should look for the following key parameters: 1. Persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg despite adequate fluid resuscitation. 2. Serum lactate level > 2 mmol/L despite adequate fluid resuscitation. Given these criteria, the correct answer is: 5. Temperature 38.4°C, urine output less than 30 ml/h, no improvement in blood pressure despite fluid challenge Explanation: • A temperature of 38.4°C indicates a fever, which is often present in septic patients. • Urine output less than 30 ml/h indicates significant hypoperfusion, a common feature in septic shock. • No improvement in blood pressure despite a fluid challenge suggests persistent hypotension, which is critical for diagnosing septic shock. This scenario matches the definition of septic shock as outlined by NICE guidelines, involving persistent hypotension and evidence of organ dysfunction despite fluid resuscitation.

Answer 63

Explanation Respiratory rate >25 breaths/min A raised respiratory rate is one of the first parameters to change in the presence of physiological stress. As such, the National Institute of Clinical Excellence (NICE) guidance identifies a raised respiratory rate as an important red flag for sepsis. Recent National Institute of Clinical Excellence (NICE) Guidance was released in 2016 in response to a UK Parliamentary inquiry examining sepsis. The ‘Time to Act’ report found failures in the recognition, diagnosis, and early management of those who died from sepsis. Efforts are now being made to improve the recognition and diagnosis of sepsis, and close monitoring and identification of abnormal physiological parameters is an important aspect of this. Systolic blood pressure <100 mmHg Systolic blood pressure <90 mmHg is identified as a red flag for sepsis. Consideration of baseline blood pressure is also an important factor and therefore a >40 mmHg fall from patient’s baseline should also be considered as a red flag in the context of sepsis. Heart rate >100 beats/min Tachycardia is an important indicator of physiological stress, however, the National Institute of Clinical Excellence (NICE) states that a heart rate >130 beats/min is a red flag for sepsis. Lactate of 1.9 mmol An elevated lactate is an indicator of reduce tissue perfusion as a result of anaerobic respiration. A measured lactate of >2.0 mmol is a ‘red flag’ for sepsis. White blood-cell count of >12 × 10 9 /l Although this would form part of a detailed review of a patient with suspected sepsis, the red flags refer specifically to physiological parameters. If abnormal, these should then trigger an in-depth review including investigations such as full blood count, blood cultures, radiological imaging as required.

Answer 64

The correct option is: 1) The commonest cause of Cushing syndrome is iatrogenic Explanation: • Iatrogenic Cushing syndrome is the most common cause of Cushing syndrome, resulting from the prolonged use of corticosteroid medications. These medications are often prescribed for conditions such as asthma, rheumatoid arthritis, and lupus. • Cushing syndrome is due to an excess of aldosterone: This statement is incorrect. Cushing syndrome is caused by an excess of cortisol, not aldosterone. Aldosterone excess is related to conditions such as Conn’s syndrome (primary hyperaldosteronism). • True Cushing syndrome is due to an adrenal adenoma: This statement is partially correct but not comprehensive. True Cushing syndrome can result from various sources, including pituitary adenomas (Cushing’s disease), ectopic ACTH production, or adrenal tumors (adenomas or carcinomas). However, adrenal adenomas are not the most common cause. • Removal of a pituitary adenoma carries a high risk of Nelson syndrome: This statement is incorrect. Nelson syndrome is a potential complication after bilateral adrenalectomy for Cushing’s disease, not after removal of a pituitary adenoma. • Cushing syndrome is seen more in men than in women: This statement is incorrect. Cushing syndrome is more commonly seen in women than in men, particularly in cases of Cushing’s disease (pituitary adenoma). Thus, the most accurate statement regarding Cushing syndrome is that the commonest cause is iatrogenic, primarily due to the use of exogenous corticosteroids.

Answer 65

The patient’s presentation is consistent with Cushing’s syndrome, which is characterized by a combination of features including central obesity, hypertension, glucose intolerance (as indicated by elevated serum glucose), and purplish striae. The clinical scenario provided points towards an underlying pathological lesion that can cause Cushing’s syndrome. Among the options listed, the most likely cause is: 1. Adrenal cortical carcinoma Explanation: Adrenal cortical carcinoma can cause Cushing’s syndrome by producing excess cortisol. The symptoms described, such as obesity, hypertension, purplish striae, and glucose intolerance, align with Cushing’s syndrome. Other options, such as anaplastic thyroid carcinoma, multinodular goiter, parathyroid adenoma, and phaeochromocytoma, do not typically present with this specific combination of symptoms. Thus, the correct answer is: 1. Adrenal cortical carcinoma Adrenal cortical carcinoma is a rare cancer carrying a poor prognosis, with most cancers metastatic at diagnosis. The female to male ratio is 2–3:1, and there is a bimodal distribution, with peak incidence in the first decade of life and a second peak in the 4th–5th decade. Metastasis is most commonly to periadrenal tissue, regional lymph nodes, bone, liver, and lungs. These are functioning tumors producing excess amounts of cortisol that are not under the control of pituitary adrenocorticotropic hormone (ACTH). Patients present with red flag symptoms such as fever, weight loss, back pain, and abdominal fullness, but also with symptoms relating to Cushing’s syndrome, as demonstrated in this scenario, and virilization syndromes. Treatment is with adrenalectomy if the tumor is confined to the adrenal gland, or chemotherapy (mostly mitotane) and/or radiotherapy if there is extensive disease. If the tumor is confined to the adrenal gland and is treated, 5-year survival is 65%. This drops to 44% for tumors with local invasion to surrounding tissues and 7% for tumors with distant metastases at diagnosis. Cushing’s syndrome involves chronic glucocorticoid excess, of which 90% are adrenocorticotropic hormone (ACTH)-dependent and 10% ACTH-independent. Causes of Cushing’s syndrome include Cushing’s disease and iatrogenic causes such as steroids. Signs of Cushing’s syndrome include: Head and neck: • Frontal balding • Moon face • Acne • Gynaecomastia in males • Plethoric complexion Trunk: • Kyphosis • Buffalo hump • Central obesity (due to altered fat distribution) • Purple striae on abdomen, breasts, and thighs • Thin, fragile skin • Predisposition to infection Limbs: • Proximal myopathy • Pathological fractures • Ankle edema (salt and water retention due to excess cortisol) • Hirsutism • Hair growth on the forearms in particular Anaplastic carcinoma of the thyroid is a rare entity, accounting for 1–2% of all thyroid cancers, a very aggressive cancer with poor prognosis. It is not known to cause symptoms relating to Cushing’s syndrome. A multinodular goiter is associated with hyperthyroidism but not Cushing’s syndrome. A parathyroid adenoma causes excessive secretion of parathyroid hormone (PTH) and results in symptoms relating to hypercalcemia and hypophosphatemia but not Cushing’s syndrome. Phaeochromocytoma is a rare tumor arising most commonly in the chromaffin cells of the adrenal medulla and resulting in increased secretion of catecholamines. Patients tend to present with severe hypertension (often resistant to multiple therapeutic agents), excessive sweating, anxiety/panic attacks, headaches, and pallor.

Answer 66

Explanation Papillary carcinoma of the thyroid Papillary carcinoma of the thyroid is the most common form of thyroid cancer accounting for 80% of cases, and of the examples in these answers, is the most common. It is a well differentiated tumour, most commonly presenting in wom en (female to male ratio of 3:1), aged 35–40. It is slow growing and arises from T4 and thyroglobulin- producing follicular cells. It can metastasise via lymphatics and can be multifocal at diagnosis. It can metastasise to the lungs. It most commonly presents as a solitary thyroid nodule. Histologically it shows stalks of epithelial cells (papillae) and in 50% of cases psammomabodies, representing calcific collections, are present. Additionally, cells show a characteristic pattern of nuclear inclusions called ‘orphan Annie eye’. Radiologically it appears as a single mass with irregular borders, found in the subscapular region. Treatment is with thyroidectomy and radioactive iodine administration for positive lymph nodes. If the tumour is confined to the thyroid gland on diagnosis, it has an excellent prognosis and a 5 year survival rate of 95%. Adrenal cortical carcinoma Adrenal cortical carcinoma is a rare cancer and prognosis depends on the extent of tumour spread at diagnosis. If the tumour is confined to the adrenal gland and is treated 5-year survival is 65%. This number drops to 44% for tumours with local invasion to surrounding tissues and 7% for tumour with distant metastases at diagnosis. Anaplastic carcinoma of the thyroid Anaplastic carcinoma of the thyroid is a rare entity, accounting for 1–2% of all thyroid cancers. It is however the most aggressive tumour and carries the worst prognosis. It most commonly affects women and patients tend to present at an older age than with other thyroid cancers, ie in the 6th–7th decade of life. Patients present with a rapidly enlarging, firm, fixed thyroid mass and symptoms of local invasion such as hoarse voice and dyspnoea or stridor. Median patient survival is 8.1 months, as anaplastic carcinoma is poorly responsive to treatment. Follicular carcinoma of the thyroid Follicular carcinoma of the thyroid is the second most common malignancy of the thyroid accounting for about 10% of all thyroid cancers. It is a well differentiated cancer, typically presenting in women aged 40–60. These tumours arise from the follicular cells of the thyroid. 5-year survival rate is over 80% for non-invasive disease. Parathyroid carcinoma Parathyroid carcinoma is a very rare malignancy, occurring equally in men and women, with men having a worse prognosis. It usually occurs after the age of 30. Disease confined to the parathyroid glands at diagnosis has a 5 -year survival rate of 88.5%.

Answer 67

Explanation Parathyroid adenoma The patient has hypercalcaemia and hypophosphataemia, pointing towards the diagnosis of primary parathyroid disease. This patient most likely has primary hyperparathyroidism, the most common cause of which is a single parathyroid adenoma (85%). Other causes include: parathyroid gland hyperplasia affecting all four parathyroid glands (10–15%), multiple parathyroid adenomas (3–5%) or a parathyroid carcinoma (1%). The adenoma produces an excess of parathyroid hormone leading to: excessive calcium resorption from bone, increased renal calcium reabsorption, increased renal phosphate excretion and increased production of 1,25-dihydroxyvitamin D3 . Therefore, blood tests reveal: a raised PTH, hypercalcaemia, hypophosphataemia and a raised vitamin D3 . Treatment of a parathyroid adenoma is by surgical removal of the parathyroid glands. For patients not fit/suitable for parathyroidectomy options for treatment include: -preventing vitamin D deficiency, bisphosphonates to protect the bones, calcimimetics to control hypercalcaemia if required. Chronic renal failure Chronic kidney failure leads to secondary hyperparathyroidism. The diseased kidney fails to convert an adequate level of vitamin D to its active form, which reduces the amount of calcium absorbed from the intestines, and fails to excrete phosphate leading to formation of calcium phosphate compounds in the circulation and a reduction in free circulating calcium. Therefore, in secondary hyperparathyroidism there is a low serum concentration of calcium and vitamin D, a high serum concentration of parathyroid hormone and a high serum phosphate. Metastatic carcinoma The two most common causes of hypercalcaemia are primary hy perparathyroidism and hypercalcaemia of malignancy. The two are generally quite difficult to differentiate. In both calcium is raised (with hypercalcaemia of malignancy causing a more dramatic hypercalcaemia) and phosphate is low. parathyroid hormone (PTH) in primary hyperparathyroidism is raised whereas in hypercalcaemia of malignancy it can be low/normal/raised depending on the mechanism involved. Given the patient’s age and the fact that the symptoms have been ongoing for several months make parathyroid adenoma a far more likely diagnosis than metastatic carcinoma. The most common cancers associated with hypercalcaemia are: breast, lung and myeloma. Pituitary adenoma A pituitary adenoma causes visual symptoms (bitemporal hemianopia), headaches and symptoms relating to the cellular origin of the adenoma. It does not commonly cause hypercalcaemia. Thyroid carcinoma Thyroid carcinoma can lead to hypercalcaemia, but this is usually seen with advanced disease.

Answer 68

Explanation Small-cell anaplastic (oat cell) carcinoma The presenting signs in this scenario point to Cushing’s syndrome, secondary to excess circulating cortisol. Given that the patient is a smoker presenting with a dry cough and lower back pain, it is most likely that the patient has small-cell lung cancer (also known as oat cell lung cancer) that has metastasised to the bones, and also secretes ectopic ACTH causing Cushing’s syndrome, as part of a paraneoplastic syndrome. This is very common with bronchogenic carcinoma. Small-cell lung cancer is strongly associated with smoking and is a neuroendocrine tumour arising in the bronchial mucosa. It is fast growing, highly metastatic, rarely operable at diagnosis and associated with a 5-year survival of less than 20%. CUSHing’s is where Cortisol is GUSHing. Cushing’s syndrome: chronic glucocorticoid excess of which 90% are ACTH-dependent and 10% ACTH-independent. Causes of Cushing’s syndrome include Cushing’s disease and iatrogenic causes such as steroids. Signs of Cushing's: Head and neck Trunk Limbs Frontal balding Kyphosis Proximal myopathy Moon face Buffalo hump Pathological fractures Acne Gynaecomastia in males Ankle oedema (salt and water rententiondue to excess cortisol) Plethoric complexion Central obesity (due to altered fat distribution) Hirsutism Purple striae on abdomen, breasts and thigs Thin, fragile skin Hair growth of the foreaems in particular Predisposition to infection 21-Hydroxylase enzyme deficiency 21-Hydroxylase enzyme deficiency, also known as congenital adrenal hyperplasia, is a condition commonly presenting at birth or early childhood with ambiguous genitalia. Extra-adrenal paraganglioma An extra-adrenal paraganglioma, also known as extra-adrenal phaeochromocytoma, are tumours producing catecholamines, such as adrenaline. The signs the patient presents with in this scenario relate to extra circulating cortisol and not catecholamines. Multiple endocrine neoplasia, type I Multiple endocrine neoplasia type I is a combination of parathyroid neoplasia, a pancreatic islet tumour and pituitary tumours. Presentation is most commonly with symptoms associated with hypercalcaemia. Other symptoms include: diarrhoea and abdominal pain in gastrinoma, hypoglycaemia in insulinomas. Depending on the place of the pituitary tumour it can present with Cushing’s disease due to over secretion of ACTH stimulating cortisol secretion. MEN 1 is however an autosomal-dominant familial disorder, therefore there must be some family history, presents usually in teenagers or patients in the 4th decade, but does not tend to present with a cough. MEN type I = Primary = pathology beginning with P Parathyroid neoplasia Pancreatic islet cell tumour (Zollinger–Ellison syndrome (50%), insulinoma (20%)) Pituitary tumours Tuberculosis Tuberculosis can present with a cough and back pain but it is not known to cause a Cushing’s syndrome.

Answer 69

Explanation 24-hour urinary vanillylmandelic acid (VMA)/homovanillic (HVA) secretion Phaeochromocytomas are rare neuroendocrine tumours arising in the chromaffin cells most commonly found in the adrenal medulla. They are associated with increased catecholamine production and tend to present with severe hypertension (often resistant to multiple therapeutic agents), excessive sweating, anxiety/panic attacks, headaches andpallor. They are usually curable if detected and treated early. If, however, they remain undiagnosed, they can lead to severe complications including death. First-line investigation for phaeochromocytoma includes a 24 h urine collection and quantification of urinary vanillylmandelic and homovanillic acids. These are byproducts of catecholamine production and are present at a low concentration in the urine of unaffected individuals. In phaeochromocytoma, however, the concentration of these molecules in the urine is significantly raised, indicating an increased production of catecholamines. Phaeochromocytomas are associated with conditions such as: multiple endocrine neoplasias 2A and 2B, von Hippel–Lindau syndrome, neurofibromatosis. Clonidine suppression test Clonidine suppression test forms the second line test in the diagnosis of phaeochromocytoma in cases where there is a high clinical suspicion but there was borderline elevation in the catecholamines, not enough to qualify for a definitive diagnosis. The test relies on the fact that clonidine is a suppressor of physiological catecholamine secretion, but has no effect over autonomous catecholamine secretion, as in phaeochromocytoma. There should be collection of urine from 21:00 on day 1 to 7:00 on day 2 occurs and catecholamines quantified. Then, on day 2, clonidine is administered and collection of urine follows from 21:00 to 7:00 of day 3. Catecholamines are quantified. In a normal individual the urine catecholamines from the second collection, ie following clonidine administration, should be greatly reduced when compared with the original collection. In patients with a phaeochromocytoma, however, clonidine is unable to suppress catecholamine release, and these remain in high concentrations in the urine. Metaiodobenzylguanidine (MIBG) scintigraphy MIBG scintigraphy is a very specific test for detecting phaeochromocytoma. Radioactive iodine-131-metaiodobenzylguanidine is administered to the patient. In a normal patient, the adrenal medulla appears to uniformly uptake the radioactive solution and its intensity is less than that of the liver uptake. For a patient with a phaeochromocytoma there is a focal area in the ad renal medulla where there is very strong and prolonged uptake of the solution. MIBG scintigraphy is not considered the first-line investigation to detect phaeochromocytoma. MIBG is useful in detecting extra - adrenal tumours or disease recurrence. Magnetic resonance imaging (MRI) scan Computed tomography (CT) and MRI scans are both sensitive in detecting phaeochromocytomas, with MRI being superior to CT scans, but are not considered the first-line investigation. These imaging modalities are used to localise t he tumour once elevated urine catecholamines are detected. Plasma noradrenaline Elevated plasma noradrenaline is a sensitive test in detecting phaeochromocytoma. This test has a high sensitivity of 96%, but a relatively low specificity of 85%, as plasma noradrenaline can be elevated in other cases such as in patients taking amitriptyline and some antipsychotic medication.

Answer 70

Explanation In children has a high relapse rate when treated with antithyroid drugs About half of the children with Graves' disease treated with antithyroid drug therapy have a complete remission, but up to 1 in 3 children suffer a relapse. Features that increase the risk of relapse include a large goitre, a high radioactive iodine uptake and a high thyroid-stimulating immunoglobulin titre. Graves' disease: also known as Graves' ophthalmopathy, thyroid-associated ophthalmopathy, dysthyroid eye disease and infiltrative eye disease. In Graves' disease the thyroid-stimulating auto-immunoglobulins are of the IgG class. Carbimazole is drug of choice for treatment throughout pregnancy Hyperthyroidism in pregnancy affects about 0.2% of the pregnant population (0.1 – 0.4%). The vast majority of these cases is caused by Grave’s disease. Carbimazole is the medication used as first line in the treatment of Graves' disease. It has however, been reported to cause severe congenital defects if used during pregnancy. Therefore, propylthiouracil is the medication of choice to treat Graves' disease during the first trimester of pregnancy. Following the first trimester, carbimazole use can resume for the remainder of the pregnancy, as propylthiouracil is associated with hepatotoxicity. Propylthiouracil inhibits the production of thyroid hormones by inhibiting the enzyme thyroperoxidase. Has equal sex incidence Hyperthyroidism caused by Graves' disease is more common in women, with an female to male ratio of 7–8:1. Is due to immunoglobulin M (IgM) thyroid-stimulating antibodies Graves' disease is the most common cause of hyperthyroidism and is an autoimmune condition mediated by IgG thyroid-stimulating antibodies, which bind the thyroid- stimulating hormone receptor, mimic the function of thyroid-stimulating hormone leading to thyroid hyperplasia and an overproduction of thyroid hormones. Is a form of toxic multinodular goitre In Graves' disease the antibodies stimulating the thyroid -stimulating hormone receptor lead to hyperplasia of the thyroid follicular cells of the thyroid gland leading to a toxic diffuse goitre.

Answer 71

Explanation It has a higher incidence in iodine-deficient regions of the world Follicular carcinoma occurs more commonly in the Caucasian population, with an incidence higher in areas of work where there is a higher incidenc e of iodine deficiency. It can be diagnosed by fine-needle aspiration cytology (FNAC) FNAC cannot differentiate between follicular carcinoma and follicular adenoma. Therefore, histological diagnosis follows a thyroid lobectomy. If follicular carcinoma is confirmed, a completion thyroidectomy should be performed. It can be monitored for recurrence by calcitonin levels In follicular carcinoma, up to 30% of patients may suffer a recurrence, which can occur decades after the primary disease. Thyroglobulin seru m levels are tested every 6–12 months to detect recurrence. A rise in thyroglobulin levels indicates recurrence. Calcitonin levels are used to monitor recurrence of medullary carcinoma. The most common presentation is a hoarse voice The most common presentation of a follicular carcinoma is a single, unilateral nodule or a thyroid mass felt on palpation of the neck. Other patients present with symptoms of difficulty swallowing, a hoarse voice or dyspnoea. It is most common at puberty Follicular carcinoma is common in all age groups, with cases reported from age 15 to 84. It is, however, more common in adults aged 40 –60.

Answer 72

Explanation Parathyroid hyperplasia MEN is a group of conditions affecting the endocrine organs and presenting with tumours in multiple endocrine organs simultaneously. MEN 2 affects 1 in 35 000 people and, of the two subtypes, the most common is MEN 2a. It is inherited in an autosomal dominant pattern, and therefore, patients have family members who are affected. MEN 2a is the association of medullary thyroid carcinoma, phaeochromocytoma and parathyroid hyperplasia. MEN 2b is the association of medullary thyroid carcinoma, mucosal neuroma and phaeochromocytoma. Pancreatic tumour Pancreatic islet tumours are seen in patients with MEN type 1. Pituitary tumour A pituitary tumour forms part of MEN syndrome type 1. Renal cell carcinoma Renal cell carcinomas are not part of the tumours seen in patients with MEN syndromes. MEN syndromes are characterised by the formation of tumours in multiple endocrine organs. Though non-endocrine tumours can coexist, they are not part of the description of the syndrome. Small cell lung carcinoma Small cell lung carcinoma is not part of the tumours seen in patients with MEN syndromes. MEN syndromes are characterised by the formation of tumours in multiple endocrine organs. Though tumours in non-endocrine organs can coexist, they are not part of the syndrome.

Answer 73

Explanation 85% A single parathyroid adenoma is the cause of primary hyperparathyroidism in about 85% of cases. Less common causes of primary hyperparathyroidism include: parathyroid gland hyperplasia involving all four glands or parathyroid carcinoma. Excess parathyroid hormone causes hypercalcaemia. 1% A parathyroid carcinoma can be the cause of primary hyperparathyroidism in about 1% of cases. 10% In 10–15% of cases of primary hyperparathyroidism, the abnormalities are caused by parathyroid hyperplasia, involving all four parathyroid glands. 30% Only 30% of patients with primary hyperparathyroidism are symptomatic. The remaining majority are usually asymptomatic, and the abnormalities associated with hyperparathyroidism are detected incidentally. 5% Three to 5% of cases of primary hyperparathyroidism are due to a double adenoma.

Answer 74

Explanation 60-70 Anaplastic thyroid carcinoma is rare (1–2% of thyroid malignancies) and the most aggressive form of primary thyroid cancer. Peak incidence is seen in adults aged 60–70 and carries a very bad prognosis, with only about 5% survival at 5 years. It is more common in women and is associated with iodine deficiency and a history of a multinodular goitre. It can metastasise to the bone, brain and lung. Patients present with a rapidly growing neck mass, usually with symptoms of compression such as dyspnoea and dysphagia. Treatment is usually palliative with doxorubicin and cisplatin but does not affect survival. 10-20 Thyroid cancer is rare in children. The rate of presentation peaks around the ages of 35–39. However, a significant amount of cases have been reported in the literature where a diagnosis of thyroid cancer is made in early adulthood. 30-40 Papillary thyroid carcinoma, which is the most common form of thyroid carcinoma, accounting for about 70% of cases, presents usually in patients aged 35 –40, with a female gender predilection. 40-50 Thyroid lymphomas most commonly affect women aged over 50 and there is an association of these cancers with Hashimoto’s thyroiditis. 80-90 Hurtle cell carcinoma, a rare form of thyroid carcinoma, has been reported in patients from the age of 20–85 years.

Answer 75

Explanation Anti-microsomal antibodies Hashimoto’s thyroiditis is an autoimmune thyroid condition where the presence of autoantibodies leads to cell destruction in the thyroid, reduced hormone output and hypothyroidism. It is the most common cause of hypothyroidism in areas where there is adequate iodine intake. It is ten times more common in women and tends to present at ages of 30 –50; however, it can present at any point during a patient’s lifetime. The most common form of autoantibodies detected in Hashimoto’s thyroiditis is antibodies against thyroid peroxidase. This is a microsomal component, an essential enzyme involved in the production of thyroid hormones, and therefore these antibodies are also referred to as anti-microsomal antibodies. Another group of commonly detected autoantibodies is anti-thyroglobulin antibodies. Hashimoto’s thyroiditis is associated with other autoimmune conditions such as pernicious anaemia and coeliac disease. It also increases the risk for developing lymphoma of the thyroid at a later stage in life. Patients tend to present with symptoms (see mnemonic) of insidious onset, gradually worsening, and with the presence of a diffuse goitre. Treatment is usually with thyroid hormo ne supplementation. Surgery is not usually required, unless there are compression symptoms from the goitre. Administration of steroids can assist in shrinking of the goitre. Anti-centromere antibodies Anti-centromere antibodies are found in limited sclerod erma disease (CREST syndrome). Anti-mitochondrial antibodies Anti-mitochondrial antibodies are associated with primary biliary sclerosis, an autoimmune condition causing liver scarring. cANCA (cytoplasmic Anti-Neutophil Cystoplasmic antibody) c-ANCA is an autoantibody directed against proteinase 3 and is found in Wegener’s granulomatosis. pANCA (perinuclear ANCA) p-ANCA is an autoantibody directed against myeloperoxidase and is associated with Churg–Strauss syndrome.

Answer 76

Explanation 20% Medullary thyroid carcinoma is a malignancy of parafollicular C cells, of neural ectodermal origin, accounting for about 5% of total primary thyroid malignancies. Medullary thyroid carcinoma is sporadic in 80% of the cases and familial in 20%. The familial form usually presents as part of the multiple endocrine neoplasia 2 syndrome (both a and b). The tumour is usually found in the upper two -thirds of the thyroid gland and can produce a variety of hormones such as calcitonin, prostaglandins and adrenocorticotrophic hormone (ACTH). Treatment is with thyroidectomy, with lymph node clearance as required. The patient in this scenario has medullary carcinoma of the thyroid, presenting as part of multiple endocrine neoplasia type 2a. 1% Medullary thyroid carcinoma can present with a thyroid nodule and local lymphadenopathy. It is important to note that metastatic medullary thyroid carcinoma presents with diarrhoea and flushes. 5% Medullary thyroid carcinoma, a malignancy arising from parafollicular C cells , accounts for 5–8% of total primary thyroid malignancy cases. 50% If a patient presents with metastatic medullary thyroid carcinoma that has spread to other parts of the body, the 10-year survival rate is < 50%, more specifically 20–40%. 75% Up to 75% of medullary thyroid carcinoma are sporadic and therefore occur in patients with no family history.

Answer 77

Explanation Primary hyperparathyroidism Given the fact that the patient is asymptomatic, the most likely diagnosis is hypercalcaemia secondary to primary hyperparathyroidism. Primary hyperparathyroidism is, in the majority of cases (85%), the result of a single parathyroid adenoma. Other causes include: parathyroid gland hyperplasia affecting all four parathyroid glands (10–15%), multiple parathyroid adenomas (3–5%) or a parathyroid carcinoma (1%). The adenoma produces an excess of parathyroid hormone, leading to: excessive calcium resorption from bone, increased renal calcium reabsorption, increased renal phosphate excretion and increased production of 1,25-dihydroxyvitamin D3 . Therefore, blood tests reveal: a raised parathyroid hormone level, hypercalcaemia, hypophosphataemia and a raised vitamin D 3 level. Treatment of a parathyroid adenoma is by surgical removal of the parathyroid glands. For patients not fit/suitable for parathyroidectomy, options for treatment include: preventing vitamin D deficiency, bisphosphonates to protect the bones and calcimimetics to control hypercalcaemia if required. Diuretic treatment Thiazide diuretics, such as bendroflumethiazide mentioned in the above scenario, block the thiazide-sensitive Na + /Cl – cotransporter found on the apical membrane of the distal convoluted tubules and therefore inhibit sodium and chloride reabsorption. Common side-effects of thiazide diuretics include: hyponatraemia, hypokalaemia, hypercalcaemia, hyperglycaemia, hyperuricaemia, gout, postural hypotension and hypochloraemic alkalosis. Hypercalcaemia caused by thiazide diuretics, however, is usually mild, and therefore unlikely to be the cause of the raised calcium concentration in this scenario. High dietary calcium intake Calcium absorption in the bowel is tightly regulated, and an increased dietary intake of calcium is not thought to be a cause of hypercalcaemia. High dietary vitamin D intake Hypervitaminosis D, ie excess vitamin D intake, can lead to hypercalcaemia. It is usually the result of taking a large amount of vitamin D supplements. In this case , the patient is only taking bendroflumethiazide and standard vitamin supplementation. Occult malignancy The two most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy. Given the patient in this scenario is asymptomatic, it is more likely that the hypercalcaemia is the result of primary hyperparathyroidism.

Answer 78

Explanation Multiple endocrine neoplasia type 2a This patient with a history of parathyroid adenoma presents with a medullary carcinoma of the thyroid. This represents an example of multiple endocrine neoplasia type 2a. This is described as the combination of: medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism. Cowden syndrome Cowden syndrome is a very rare autosomal dominant condition, also referred to as multiple hamartoma syndrome, associated with the presence of multiple non -cancerous growths called hamartomas. It increases the susceptibility of individuals affected to develop some forms of cancers such as thyroid, endometrial, colorectal and renal cancers and melanoma. Familial medullary carcinoma of the thyroid Familial medullary carcinoma of the thyroid is a subtype of multiple endocrine neoplasia type 2 where patients dev elop medullary carcinoma of the thyroid but have a lower probability of having a parathyroid adenoma or a phaeochromocytoma. This accounts for 10–20% of all multiple endocrine neoplasia type 2 cases. Multiple endocrine neoplasia type 1 Multiple endocrine neoplasia type I describes the combination of parathyroid hyperplasia, pancreatic islet cell tumours and pituitary tumours. Multiple endocrine neoplasia type 2b Multiple endocrine neoplasia type 2b describes the combination of a medullary thyroid carcinoma, mucosal neuromas, phaeochromocytoma and marfanoid body habitus.

Answer 79

Explanation Autoimmune thyroiditis (Hashimoto’s thyroiditis) Hashimoto’s thyroiditis is an autoimmune thyroid condition where the presence of autoantibodies leads to cell destruction in the thyroid, reduced hormone output and hypothyroidism. It is the most common cause of hypothyroidism in areas where there is adequate iodine intake. It is ten times more common in women and tends to present at ages 30–50; however, it can present at any point during a patient’s lifetime. The most common form of autoantibodies detected in Hashimoto’s thyroiditis is antibodies against thyroid peroxidase. This is a microsomal component, an essential enzyme involved in the production of thyroid hormones, and therefore these antibodies are also referred to as anti-microsomal antibodies. Another group of commonly detected autoantibodies is anti-thyroglobulin antibodies. Patients tend to present with symptoms of insidious onset, gradually worsening, and with the presence of a goitre. It is a lymphocytic infiltration of the gland, with subsequent fibrosis, leading to diffuse enlargement. The goitre associated with Hashimoto’s thyroiditis is symmetrical, rubbery in texture and painless. Hashimoto’s thyroiditis is associated with other autoimmune conditions such as pernicious anaemia and coeliac disease. It also increases the risk for developing lymphoma of the thyroid at a later stage in life. Treatment is usually with thyroid hormone supplementation. Surgery is not usually required, unless there are compression symptoms from the goitre. Administration of steroids can assist in shrinking of the goitre. Acute suppurative thyroiditis Acute suppurative thyroiditis is a rare condition caused by bacterial infection of the thyroid gland that tends to affect patients with anatomical defects or concurrent thyroid disease. Graves’ disease Graves’ disease presents with a toxic, diffuse goitre and is associated with thyroid - stimulating antibodies that bind to the thyroid -stimulating hormone receptors. Riedel’s thyroiditis Riedel’s thyroiditis is a rare condition. It describes the chronic fibrosis of the thyroid gland, resulting in a rapidly growing, painful, hard and fixed thyroid mass. Fibrosis can extend outside the thyroid gland to surrounding structures. Subacute thyroiditis (De Quervain’s thyroiditis) De Quervain’s thyroiditis (or subacute thyroiditis) is usually viral in origin, and patients report a preceding viral illness such as mumps, measles, influenza, etc.

Answer 80

Explanation Primary hyperparathyroidism The most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy. In this case, given the patient has mild hypercalcaemia, it is more likely that this is due to primary hyperparathyroidism. Most primary hyperparathyroidism (85%) is caused by the presence of a single parathyroid adenoma. The adenoma produces an excess of parathyroid hormone (PTH), leading to: excessive calcium resorption from bone, increased renal calcium reabsorption, increased renal phosphate excretion and increased production of 1,25-dihydroxyvitamin D3 . Therefore, blood tests reveal: a raised PTH level, hypercalcaemia, hypophosphataemia and a raised vitamin D 3 level. A mildly raised alkaline phosphatase level is also seen in primary hyperparathyroidism. Treatment of a parathyroid adenoma is by surgical removal of the parathyroid glands. For patients not fit/suitable for parathyroidectomy, options for treatment include: preventing vitamin D deficiency, bisphosphonates to protect the bones and calcimimetics to control hypercalcaemia if required. Secondary hyperparathyroidism In chronic renal disease, there is a reduction in the secretion of phosphate, with reduced estimated glomerular filtration rate (eGFR). The resulting hyperphosphataemia stimulates PTH secretion and causes formation of calcium and phosphate crystals, leading to hypocalcaemia. Therefore, in secondary hyperparathyroidism, biochemical findings include: raised PTH, low calcium, raised phosphate and raised alkaline phosphatase levels. Tertiary hyperparathyroidism Following a long-standing period of secondary hyperparathyroidism or following a renal transplant, tertiary hyperparathyroidism can arise. Following a period of parathyroid gland stimulation, the parathyroid glands continue to secrete PTH autonomously and result in: raised PTH levels, hypercalcaemia and hyperphosphataemia. Osteoporosis Osteoporosis leaves calcium, phosphate and PTH levels unaffected. Alkaline phosphatase is normal. Paget’s disease Paget’s disease of the bone is associated with excessive bone breakdown and formation, with subsequent disorganised bone remodelling. This results in weakened bones associated with pain and fractures. In Paget’s disease, calcium, phosphate and PTH levels remain unaffected. Alkaline phosphatase level is markedly raised in Paget’s disease.

Answer 81

Explanation Liver cirrhosis Gynaecomastia, defined as ‘benign proliferation of male breast tissue’, is caused by a disruption in the oestrogen:testosterone ratio, in favour of oestrogen. It can be secondary to some medication therapy, most commonly spironolactone. In liver disease, there is an increased activity of aromatase enzyme, leading to conversion of androgens to oestrogens. Additionally, the resulting high oestrogenic state increases the production of sex hormone-binding globulin (SHBG) in the liver, leading to a further decrease in serum free testosterone levels. This tip in the balance in favour of oestrogen leads to gynaecomastia, as the oestrogens induce ductal hyperplasia and proliferation of breast tissue. Patients with alcoholic liver disease are at a higher risk for gynaecomastia because phyto-oestrogens found in alcohol are direct inhibitors of testosterone. Low-dose, occasional cimetidine Cimetidine is a histamine receptor blocker used in the treatment of gastro-oesophageal reflux disease and in the prevention of gastric ulcers. Common side-effects of cimetidine include dizziness, drowsiness, diarrhoea and headache. It can rarely cause gynaecomastia or a breast lump, as it affects the cytochrome P450system in the liver and leads to raised serum oestrogens. This can lead to gynaecomastia but is dose-dependent and seen in high doses and prolonged treatment. Oral corticosteroids Oral corticosteroids can lead to fat redistribution but are not known to cause gynaecomastia. Parathyroid gland tumours Parathyroid gland tumours present with signs relating to hypercalcaemia such as polyuria, polydipsia, renal stones, constipation and mental disturbances (depression). Regular bromocriptine therapy Bromocriptine is an ergot derivative and a potent dopamine receptor agonist. It is used in the treatment of Parkinson’s disease and also to suppress lactation in the treatment of galactorrhoea or in women following an intrauterine fetal death, by inhibiting secretion of prolactin. Known side-effects include: nausea, vomiting, constipation, hypotension, confusion and lethargy. It is not known to cause gynaecomastia.

Answer 82

Explanation 24-hour urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) secretion Phaeochromocytomas are rare neuroendocrine tumours arising in the chromaffin cells, most commonly found in the adrenal medulla. They are associated with increased catecholamine production and tend to present with severe hypertension (often resistant to multiple therapeutic agents), excessive sweating, anxiety/panic attacks, headaches and pallor. They are usually curable if detected and treated appropriately. If, however, they remain undiagnosed, they can lead to severe complications, including death. The first-line investigation for phaeochromocytomas includes a 24 -hour urine collection and quantification of urinary VMA and HVA. These are by-products of catecholamine production and are present in low concentrations in the urine of unaffected individuals. In phaeochromocytoma, however, the concentration of these molecules in the urine is raised, indicating an increased production of catecholam ines. Phaeochromocytomas are associated with conditions such as multiple endocrine neoplasia types 2a and 2b, von Hippel–Lindau syndrome and neurofibromatosis. Clonidine suppression test The clonidine suppression test forms the second -line test in the diagnosis of phaeochromocytoma in cases where there is a high clinical suspicion but there is borderline elevation in the catecholamines, not enough to qualify for a definitive diagnosis. The test relies on the fact that clonidine is a suppressor of physiologi cal catecholamine secretion but has no effect over autonomous catecholamine secretion, like in the case of phaeochromocytoma. Collection of urine from 2100 h on day 1 to 0700 h on day 2 occurs and catecholamines quantified. Then, on day 2, clonidine is administered and collection of urine follows from 2100 h to 0700 h on day 3. Catecholamines are quantified. In a normal individual, the urine catecholamines from the second collection, ie following clonidine administration, should be greatly reduced when comp ared to the original collection. In patients with phaeochromocytoma, however, clonidine is unable to suppress catecholamine release, and these remain in high concentrations in the urine. MIBG scintigraphy MIBG scintigraphy is a very specific test for detecting phaeochromocytoma. Radioactive iodine-131-metaiodobenzylguanidine is administered to the patient. In a normal patient, the adrenal medulla appears to uniformly uptake the radioactive solution and its intensity is less than that of liver uptake. In the case of a patient with phaeochromocytoma, there is a focal area in the adrenal medulla where there is very strong and prolonged uptake of the solution. MIBG scintigraphy is not considered the first-line investigation to detect phaeochromocytoma. MIBG is u seful in detecting extra- adrenal tumours or disease recurrence. Magnetic resonance imaging (MRI) Computerised tomography (CT) and MRI scans are both sensitive in detecting phaeochromocytomas, with MRI being superior to CT, but are not considered the first - line investigation. These imaging modalities are used to localise the tumour once elevated urine catecholamines are detected. Plasma noradrenaline Elevated plasma noradrenaline is a sensitive test in detecting phaeochromocytoma. This test has a high sensitivity of 96%, but a relatively low specificity of 85%, as plasma noradrenaline can be elevated in other cases such as in patients taking amitriptyline and some antipsychotic medication.

Answer 83

Explanation Tertiary hyperparathyroidism The patient presents with symptoms relating to hypercalcaemia that is caused by tertiary hyperparathyroidism. Following a long -standing period of secondary hyperparathyroidism, such as that occurring during renal failure, tertiary hyperparathyroidism can arise. This is commonly seen following renal transplantation to treat renal failure. Due to the prolonged stimulation that has occurred in the parathyroid glands, in response to the relative serum hypocalcaemia caused by renal failure, the glands continue to secrete PTH autonomously and inappropriately, even after the correction of hypocalcaemia. As in the above scenario, this results in: raised PTH levels, hypercalcaemia and hyperphosphataemia. Alkaline phosphatase level is mildly raised in all forms of hyperparathyroidism but can also be normal. Primary hyperparathyroidism Primary hyperparathyroidism is most commonly due to a parathyroid adenoma and results in raised parathyroid hormone (PTH) levels, hypercalcaemia (usually mild to moderate), hypophosphataemia and raised vitamin D 3 levels. A mildly raised alkaline phosphatase level is also seen in primary hyperparathyroidism. Secondary hyperparathyroidism In chronic renal disease, there is a reduction in the secretion of phosphate, with reduced estimated glomerular filtration rate (eGFR). The resulting hyperphosphataemia stimulates PTH secretion and causes the formation of calcium and phosphate crystals, leading to hypocalcaemia. Therefore, in secondary hyperparathyroidism, biochemical findings include: raised PTH, low calcium, raised phosphate and raised alkaline phosphatase levels. Osteoporosis Osteoporosis leaves calcium, phosphate and PTH levels unaffected. Alkaline phosphatase level is normal. Paget’s disease Paget’s disease of the bone is associated with excessive bone breakdown and formation, with subsequent disorganised bone remodelling. This results in weakened bones associated with pain and fractures. In Paget’s disease, calcium, phosphate and PTH levels remain unaffected. Alkaline phosphatase level is markedly raised in Paget’s disease.

Answer 84

Squamous cell carcinoma of the lung is responsible for hypercalcaemia and low serum phosphate levels. Ten percent of all lung cancers produce hormones or peptides involved in paraneoplastic syndromes. One of the most commonly encountered paraneoplastic syndromes is humoral hypercalcaemia of malignancy, seen with squamous cell carcinoma of the lung. This cancer produces parathyroid hormone-related peptide, which mimics the action of parathyroid hormone. Consequently, it causes hypercalcaemia and hypophosphataemia, as parathyroid hormone stimulates calcium resorption from bone, renal calcium reabsorption, renal phosphate excretion, and increased production of 1,25-dihydroxyvitamin D3. Osteoclastoma is normally a benign primary bone tumor and does not typically cause hypercalcaemia and hypophosphataemia. Prostate cancer can metastasize to the bones and lead to the release of calcium and phosphate into the bloodstream, resulting in hypercalcaemia and hyperphosphataemia. Transitional cell carcinoma of the bladder may metastasize to the bones. Metastatic cancerous bone lesions can result in the release of mineralized calcium and phosphate into the bloodstream, leading to hypercalcaemia and hyperphosphataemia. Basal cell carcinoma rarely associates with hypercalcaemia. Hypercalcaemia is more commonly associated with squamous cell carcinoma of the skin and melanoma, but not with basal cell carcinoma.

Answer 85

Thyroxine deficiency, or hypothyroidism, is most likely to be affecting the patient in this scenario. It can be either primary (due to the thyroid gland not producing enough thyroxine) or secondary (where the thyroid gland is normal but does not receive enough TSH for stimulation of hormone production, suggesting a pituitary problem). Thyroxine is involved in the stimulation of cell metabolism and thermoregulation. Deficiency presents with a variety of symptoms relating to metabolic and mental slowness. If hypothyroidism is confirmed, it is treated with hormone replacement with a synthetic T4 molecule and monitored by regular TSH serum levels. Somatostatin is a peptide hormone produced in the delta cells of the islets of Langerhans in the pancreas and the ventromedial nucleus of the hypothalamus. It inhibits the production of glucagon and insulin in the pancreas and the secretion of gastric acid, gastrin, and secretin. In the pituitary, it inhibits the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone (TSH). Somatostatin overproduction can result in diabetes, gallstones, fat intolerance in the diet, steatorrhea, and diarrhea. Somatostatin deficiency is very rare; only a few cases have been reported in the literature. However, decreased cerebrospinal fluid levels of somatostatin have been documented in patients with Alzheimer’s disease. Cholecystokinin is a hormone produced by the I cells of the duodenum, which has multiple functions. It is released in response to the presence of fat in the duodenum and inhibits gastric emptying, promotes pancreatic hormone secretion, and promotes contraction of the gall bladder and relaxation of the sphincter of Oddi. Deficiency of cholecystokinin is extremely rare and usually manifests as part of a polyglandular syndrome, resulting in malabsorption. Testosterone deficiency presents with loss of libido, erectile dysfunction, low semen volume, fatigue, hair loss, decrease in bone and muscle mass, with a corresponding increase in body fat, as well as mood changes. Insulin deficiency presents with features of diabetes mellitus such as polyuria, polydipsia, increased thirst, and loss of weight. Remember, hypothyroidism is ten times more common in women than men and occurs mainly in middle life.

Answer 86

Explanation Hyperparathyroidism The patient presents symptomatic of hypercalcaemia with a renal stone, dyspepsia and depression. Given the patient is young and fit, the most likely cause of the hypercalcaemia seen in this scenario is primary hyperparathyroidism. However, as hypercalcaemia is commonly due to malignancy, this needs to be excluded. Primary hyperparathyroidism is, in the majority of cases (85%), the result of a single parathyroid adenoma. Other causes include: parathyroid gland hyperplasia affecting all four parathyroid glands (10–15%), multiple parathyroid adenomas (3–5%) or a parathyroid carcinoma (1%). The adenoma produces an excess of parathyroid hormone, leading to excessive calcium resorption from bone, increased renal calcium reabsorption, increased renal phosphate excretion and increased production of 1,25-dihydroxyvitamin D3 . Therefore, blood tests reveal: a raised parathyroid hormone level, hypercalcaemia, hypophosphataemia and a raised vitamin D 3 level. Treatment of a parathyroid adenoma is by surgical removal of the parathyroid glands (parathyroidectomy). For patients not fit/suitable for parathyroidectomy, options for treatment include: preventing vitamin D deficiency, bisphosphonates to protect the bones and calcimimetics to control hypercalcaemia if required. Actinomycosis infection Actinomycosis infection is a bacterial infection characterised by a suppurative granulomatous inflammation and formation of multiple abscesses, discharging sulfur - containing granules. It commonly affects the thorax, abdomen or face and neck (cervicofacial). Abdominal actinomycosis presents with sensation of a mass, fever, weight loss, fatigue, nausea and vomiting. Blood biochemistry is usually normal, with the exception of a raised alkaline phosphatase level in the case of hepatic actinomycosis. Ectopic parathyroid hormone Ectopic parathyroid hormone secretion is usually secondary to malignancy as part of a paraneoplastic syndrome. Even though hypercalcaemia of malign ancy is a common cause of hypercalcaemia and needs to be excluded in this case, given the patient is young and fit, the most likely cause of the biochemical picture seen is primary hyperparathyroidism. Hypoparathyroidism Hypoparathyroidism results in parathyroid hormone deficiency and subsequently in hypocalcaemia. Vitamin D deficiency Vitamin D deficiency would result in hypocalcaemia, as vitamin D is essential for the absorption of dietary calcium in the gastrointestinal system.

Answer 87

Explanation Decreased TSH, raised free T4, raised free T3 Graves’ disease is an autoimmune condition leading to a diffuse enlargement of the thyroid, hyperstimulation and increased production of thyroid hormones. In Graves’ disease, there are thyrotropin receptor antibodies (immunoglobulin G (IgG) antibodies) circulating in the blood, stimulating the TSH receptor and promoting the production of thyroid hormones. There is therefore increased free T3 and T4; this acts as a negative feedback on the pituitary, suppressing the production of endogenous TSH, which is why, in Graves’ disease, TSH is low. Raised thyroid-stimulating hormone (TSH), raised free T4, raised free T3 This can be seen in the presence of a TSH-secreting pituitary tumour, amiodarone therapy or acute psychiatric illness. Normal TSH, raised free T4, decreased T3 Beta blocker therapy interferes with the conversion of T4 to T3 and can therefore cause the above picture. Decreased TSH, decreased free T4, decreased free T3 This clinical scenario describes patients who have recently been treated for hyperthyroidism or patients with congenital TSH or thyrotropin-releasing hormone deficiency. Raised TSH, normal free T4, normal free T3 This is the presentation of subclinical hypothyroidism.

Answer 88

Explanation Vitamin D deficiency Vitamin D is essential for the absorption of calcium in the gastrointestinal tract. Therefore, a deficiency in vitamin D can cause reduced absorbed calcium from the diet and lead to hypocalcaemia. Secondary hyperparathyroidism is a condition that results in stimulation of PTH secretion due to a reduction in serum calcium concentration. It is most commonly seen in chronic renal failure where there is reduced vitamin D activation and reduced phosphate excretion. The result is a reduction in calcium absorption from the gastrointestinal tract, but also binding of the free calcium to phosphate, causing the formation of calcium phosphate compounds. These both lead to hypocalcaemia and stimulation of the parathyroid glands to produce PTH, in an effort to increase calcium concentration in the serum. Acute renal failure Hypocalcaemia is often seen with chronic renal failure, as part of secondary hyperparathyroidism. Multiple endocrine neoplasia type 1 (MEN 1) MEN 1 is associated with a parathyroid adenoma, leading to hypercalcaemia through the mechanism of primary hyperparathyroidism, a pancreatic islet cell tumour and a pituitary tumour. Parathyroid adenoma A parathyroid adenoma leads to primary hyperparathyroidism, through excess secretion of parathyroid hormone (PTH) from the adenoma. Biochemical features of primary hyperparathyroidism include: hypercalcaemia, hypophosphataemia, raised PTH level and raised vitamin D 3 level. There is sometimes raised alkaline phosphatase level as well. Pregnancy Pregnancy is a cause of primary hyperparathyroidism, resulting from hyperplasia of the parathyroid glands.

Answer 89

Explanation Avascular necrosis of bone Avascular necrosis of bone and osteoporosis are well -recognised side-effects of long- term corticosteroid therapy, irrespective of its mode of administration. This is a multifactorial process, characterised by interruption of the vascular supply to the bone, leading to marrow, medullary bone and cortex necrosis. Most commonly, affected bones are those with a terminal blood supply, and necrosis occurs in the epiphysis. These include the femur, humerus, carpals and talus. Factors that increase the risk include: female gender, high daily dose and prolonged therapy. It is thought that concurrent autoimmune disease also increases the risk of developing avascular necrosis with corticosteroid therapy. Hepatotoxicity Glucocorticoid therapy is not known to have toxic effects on the liver. Hyperkalaemia Glucocorticoids exert several effects on the kidneys. They increase water diuresis and glomerular filtration rate, while causing hypernatraemia and hypokalaemia, due to an increase in sodium retention and potassium secretion. Bone marrow suppression Initiating corticosteroid therapy can cause a refl ex leukocytosis, predominantly affecting polymorphonuclear leukocytes, ie neutrophils. Prolonged therapy can lead to suppression of the immune system and increase the risk for infection. Steroid therapy is not, however, a common cause of bone marrow suppression, with common causes being cytotoxic chemotherapy or immunosuppressants such as azathioprine. Hypotension Glucocorticoid therapy is associated with hypertension, and not hypotension. Steroids stimulate the mineralocorticoid receptor in the kidney, resulting in sodium and water resorption, increase in intravascular volume and therefore increase in blood pressure.

Answer 90

Explanation Thyrotoxicosis Thyrotoxicosis is associated with hypercalcaemia. Thyroid hormones directly stimulate bone resorption leading to decalcification and demineralisation leading to an increase in serum calcium. This mechanism is not associated with hyperparathyroidism. However, there is a significant proportion of patients with hyperthyroidism that have concomitant primary hyperparathyroidism, leading to hypercalcaemia. It is estimated that hypercalcaemia is seen in 25% of patients with proven hyperthyroidism. The patient will need other tests such as: thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) as well as free T4 / T 3 to confirm the diagnosis. Toxic goitres tend to most commonly present around the 4 th -5 th decade of life, fitting with the age of the patient in this scenario. Addison’s disease Addison’s disease is a known cause of hypercalcaemia. It is due to adrenocortical insufficiency leading to glucocorticoid and mineralocorticoid deficiency. As a result of the mineralocorticoid (aldosterone) deficiency there is sodium loss in the kidneys and potassium retention. Therefore Addison’s disease is associated with hyponatraemia an hyperkalaemia. With a normal sodium and potassium in this scenario the cause of the hypercalcaemia is not Addison’s disease. Chronic renal failure In this scenario the patient’s renal function is completely normal, with a normal urea and creatinine, ruling out chronic renal failure. Chronic renal failure is a common cause of secondary hyperparathyroidism presenting with a raised parathyro id hormone, hypocalcaemia and hyperphosphataemia. This is because in chronic renal disease there is a reduction in the excretion of phosphate and a low glomerular filtration rate. The retained phosphate creates phosphate–calcium compounds in the blood leading to a low free serum calcium. Diabetes mellitus Patients with diabetes mellitus are more likely to develop hypocalcaemia, as a result of diabetic renal disease, rather than hypercalcaemia. However, in some cases there is co - existence of hyperparathyroidism and diabetes mellitus. Sarcoidosis Even though sarcoidosis is a cause of hypercalcaemia, it is unlikely in this scenario given the mention of a normal chest radiograph. Sarcoidosis presents with hilar and mediastinal node enlargement as well as parench ymal lung disease, both evident on chest radiography.

Answer 91

Explanation Hypocalcaemia and reduced conversion of vitamin D to 1,25-dihydroxycholecalciferol Post-operative hypocalcaemia is the most common complication encountered following a thyroidectomy. This is caused by acute parathyroid insufficiency from the reduction in the parathyroid parenchymal tissue, as often some or all of the parathyroid glands are removed during a total thyroidectomy. This results in a reduced level of synthesis of parathyroid hormone and leads to a reduction in bone resorption, reduced conversion of vitamin D to 1,25-dihydroxycholecalciferol in the kidney are a resulting hypocalcaemia due to a reduced absorption of dietary calcium in the gastrointestinal tract. The resulting hypocalcaemia presents with paraesthesia in the extremities and peri-orally (circumoral), abdominal cramps, tetany and posi tive Chvostek’s and Trousseau’s signs. Hypercalcaemia and overall reduced osteoclast activity The patient presents with hypocalcaemia. Hypocalcaemia and overall increased bone resorption and reduced parathyroid hormone secretion Increased bone resorption is the result of increased action of the parathyroid hormone (PTH) and leads to hypercalcaemia. In hypoparathyroidism, there is a reduced level of parathyroid hormone, with an overall decrease in bone resorption and hypocalcaemia. Hypocalcaemia and reduced renal reabsorption of calcium through the action of 1,25 - dihdroxycholecalciferol Absorption of calcium through the action of 1,25 -dihydroxycholecalciferol occurs in the gastrointestinal tract and not in the renal tract. Hypocalcaemia and increased bone resorption Increased bone resorption is the result of increased action of parathyroid hormone (PTH) and leads to hypercalcaemia and not hypocalcaemia.

Answer 92

Explanation 1,25-Dihydroxyvitamin D deficiency This patient presents with fragility fractures secondary to osteoporosis. Osteoporosis, is a disease characterised by reduced bone strength leading to increased risk of fractures and it most commonly occurs in post-menopausal women due to a variety of causes that favour bone catabolism rather than bone mass increases and build up. Osteoporosis presents with unusual fractures at low impact eg vertebral, neck of femur and Colles’ fractures. Vitamin D deficiency is one of the common causes leading to osteoporosis and fragility fractures. Inadequate 1,25-dihydroxyvitamin D (1,25-dihydroxycholecalciferol) can result either from inadequate exposure to sunlight, inadequate intake of vitamin D. Vitamin D deficiency in children results in rickets, and in adults in osteomalacia, both of which are characterised by a reduced mineral density of the bones making bones brittle and fragile. Additionally, in the absence of vitamin D causes a reduced absorption of calcium from the gastrointestinal system, leading to serum hypocalcaemia which is detected by the parathyroid glands that stimulate production of parathyroid hormone. The latter leads to an increase in bone resorption. Bones therefore lose their calcium and become demineralised and brittle. Management of osteoporosis is multifaceted. It includes lifestyle changes such as adequate calcium and vitamin D intake, smoking cessation, introduction of exercise in daily activities, reduction in alcohol consumption and falls prevention strategies. Pharmacological treatments include calcium and vitamin D supplementation, bisphosphonates and calcitonin. Hypothyroidism In hyperthyroidism, the excess circulating thyroxine, increases the rate of bone metabolism and resorption. Hypothyroidism however does not have a similar effect. Bisphosphonates Bisphosphonates are used in the treatment of osteoporosis as they act by promoting osteoclast apoptosis and slowing bone resorption. They reduce the risk of fragility fractures in post-menopausal women with osteoporosis. The most commonly used bisphosphonate is alendronic acid. Calcitonin Calcitonin, a hormone produced by the C-cells of the thyroid gland, in response to hypercalcaemia reduces the serum calcium level and opposes the effect of parathyroid hormone. It inhibits the resorption of bone by inhibiting osteoclast activity. Therefore, it helps in maintaining adequate bone calcification and is being used as a treatment for patients with osteoporosis. Hormone replacement therapy (HRT) Hormone replacement therapy, in the form of oestrogen only or oestrogen – progesterone, slows bone metabolism and increases bone mineral density and reduces the risk of a bone fragility fracture. However, once HRT is discontinued, there is accelerated bone metabolism with a rapid decrease in bone mineral density and the protective function of HRT that has preceded is lost. Osteoporosis is more common in post-menopausal women due to the loss of the oestrogenic protective factors.

Answer 93

Explanation Sweating, paroxysmal hypertension and increased metabolic rate Phaeochromocytomas are rare tumours, most commonly arising in the chromaffin cells of the adrenal medulla and resulting in increased secretion of catecholamines (adrenaline, noradrenaline, dopamine, occasionally). Adrenaline is a potent stimulator of the sympathetic system and increases the metabolic rate causing sweating. It binds to a- and b-adrenoceptors. Binding to a-adrenergic receptors brings about effects such as vasoconstriction, elevation in blood pressure, glycogenolysis and gluconeogenesis. Binding to b-adrenergic receptors brings about tachycardia and increased contractility of the heart. Phaeochromocytoma is treated by adrenalectomy, however, adequate a- and b-adrenoceptor blockage is necessary before surgery. Alpha-receptor blockage controlsblood pressure and prevents a hypertensive crisis, whereas b -receptor blockage controls the heart rate. Adequate a-adrenoceptor blockage is necessary first, as unopposed alpha adrenergic activity that can occur during b-blockade may precipitate a hypertensive crisis. Decreased sweat production, paroxysmal hypertension and decreased metabolic rate Phaeochromocytoma is associated with increased sweat production, paroxysmal hypertension and increased metabolic rate. Sweating, paroxysmal hypertension and decreased metabolic rate Although phaeochromocytomas can occur in any age their peak incidence has been reported in patients between the age of 30–50. Sweating, paroxysmal hypotension and decreased metabolic rate Occasionally patients with phaeochromocytoma can have postural hypotension during an episode due to the high volume of fluid lost from excessive sweating. Sweating, paroxysmal hypotension and increased metabolic rate Phaeochromocytomas typically present with a tetrad of headaches, palpitations, severe hypertension and excessive sweating. It is important to note that the symptoms are not constant and are episodic, varying in frequency and duration over the course of the day. As the tumour size increases, episodes become more frequent and prolonged.

Answer 94

Explanation Hypocalcaemia Hypocalcaemia suggests that there is at least in part a longstanding element to the renal failure seen in this patient. This is due to two mechanisms: firstly there is reduced renal synthesis of 1,25-dihydrocholecalciferol, the active form of vitamin D, necessary in the absorption of dietary calcium in the gastrointestinal system. Secondly, as the glomerular filtration rate (GFR) drops, and the filtering ability of the kidney deteriorates, less phosphate is excreted in the urine. The circulating phosphate forms calcium-phosphate compounds, reducing the amount of free circulating calcium. These two mechanisms lead to hypocalcaemia. Hyperkalaemia Hyperkalaemia can be the result of both acute and chronic renal failure and occurs due to reduced excretion of potassium and accumulation in the body. Hyperuricaemia Hyperuricaemia is the result of both acute and chronic renal failure and occurs secondary to the reduced ability of the kidney to filter and excrete waste products from the blood, leading to accumulation of these in the blood. Hyponatraemia Hyponatraemia can be a feature of both acute and chronic renal failure and occurs mainly due to a continued fluid intake while there has been a reduced ability to excrete this fluid. Low serum bicarbonate concentration Low serum bicarbonate is a feature of metabolic acidosis that can precipitate both acute and chronic renal failure.

Answer 95

Explanation TSH Thyroid-stimulating hormone (TSH) is produced by the thyrotrope cells in the anterior pituitary. The anterior pituitary gland produces six hormones. Testosterone Testosterone is produced in the Leydig cells of the testicles, under the influence of luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced from the anterior pituitary gland. Oxytocin Oxytocin is produced by the posterior pituitary gland and causes uterine contraction, milk ejection and labour. CRH Corticotrophin releasing hormone (CRH) is produced by cells in the paraventricular nucleus of the hypothalamus and stimulates corticotropes in the anterior pituitary to produce ACTH. ADH Antidiuretic hormone (ADH), also known as vasopressin, is secreted form the posterior pituitary gland and increases water permeability of the renal collecting ducts and distal convoluted tubules leading to increased water reabsorption in the kidneys.

Answer 96

Explanation Cholesterol Hypothyroidism is the second most common cause of hypercholesterolaemia after diet. Thyroid hormones are inducers of HMG –CoA reductase enzyme, the first step in cholesterol synthesis, but also T 3 upregulates low-density lipoprotein (LDL) receptors in the liver, where LDL-cholesterol binds and catabolism occurs. Therefore, in hypothyroidism, even though there is a reduction in cholesterol synthesis there is also a downregulation of LDL receptors and catabolism of cholesterol in the liver, leading to an overall increase in the serum level of cholesterol. Hypothyroid patients are at an increased risk of developing cardiovascular disease and their lipid profile should be carefully monitored. Albumin Thyroid hormones promote albumin catabolism, while some of the circulating thyroid molecules travel in the blood bound to albumin. Therefore in hypothyroidism, there is decreased albumin catabolism, leading to more albumin available for glycosylation. It is the glycated albumin level that is raised in hypothyroid patients. Similarly in hyperthyroidism, the glycated albumin levels are reduced as albumin catabolism is induced. rT3 rT3 , is reverse tri-iodothyronine and is an inactive molecule formed by the deiodination of thyroxine. It differs from tri-iodothyronine in the positions that the iodine atoms are attached to the aromatic rings. The concentration of rT 3 in the serum tends to follow that of T4 . It is therefore reduced in hypothyroidism and raised in hyperthyroidism. Iodide Iodide is reduced in hypothyroid disease. Thyroid stimulating immunoglobin Thyroid-stimulating immunoglobulin is an antibody that binds the thyrotropin (TSH) receptor on the thyroid gland, stimulating thyroid hormone production. These are diagnostic of Grave’s disease, a form of hyperthyroidism.

Answer 97

Explanation Increased osteoclastic activity A parathyroid adenoma leads to increased production of parathyroid hormone (PTH) the actions of which aim to increase serum calcium. This is done by acting on the bone, gastrointestinal system and the kidney. In the bone PTH stimulates the activity of osteoclasts in the bone leading to increased bone resorption. In the kidney it promotes the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol, the active form of vitamin D, necessary to absorb dietary calcium from the gut. In the kidney PTH also promotes excretion of phosphate in the urine at the renal proximal convoluted tubule and calcium reabsorption in the distal convoluted tubule. Decreased osteoclastic activity A parathyroid adenoma produces parathyroid hormone (PTH) that stimulates osteoclastic activity. Decreased urinary phosphate excretion A parathyroid adenoma producing parathyroid hormone (PTH) causes increased urinary phosphate excretion in the proximal convoluted tubule. Hypocalcaemia A parathyroid adenoma produces parathyroid hormone (PTH) that causes hypercalcaemia, hyperchloraemia and hypophosphataemia. Increased osteoblastic activity A parathyroid adenoma produces parathyroid hormone (PTH) that promotes the action of osteoclasts, leading to bone resorption.

Answer 98

Explanation Periorbital swelling and lethargy A raised TSH combined with a low T 3 resin uptake, and a low T4 , are characteristics of hypothyroidism. Hypothyroidism is associated with a dull facial expression, periorbital swelling secondary to mucopolysaccharide infiltration, decreased adrenergic drive – causing bradycardia/cold intolerance/lethargy, as well as reduced basal metabolic rate leading to decreased appetite and weight gain. Patients also experience mental slowness, depression and forgetfulness. Periorbital swelling in hypothyroidism needs to be distinguished to exophthalmos in Grave’s disease which is proptosis due to increased retro-orbital tissue. Anxiety Anxiety is seen in hyperthyroid patients. The results of the thyroid function tests above indicate that the patient is in a hypothyroid state. Increased body temperature Increased body temperature is a sign seen in hyperthyroid patients. The results of the thyroid function tests above indicate that the patient is in a hypothyroid state. Palpitations Palpitations are experienced by hyperthyroid patients. The results of the thyroid function tests above indicate that the patient is in a hypothyroid state. Tachycardia Tachycardia is a sign associated with hyperthyroidism. The results of the thyroid function tests above indicate that the patient is in a hypothyroid state.

Answer 99

Explanation Graves’ disease Graves’ disease is the most common cause of hyperthyroidism and is an autoimmune condition mediated by thyroid-stimulating hormone antibodies. These bind the thyroid- stimulating hormone receptor and mimic the action of endogenous TSH, leading to hyperplasia of the follicular cells of the thyroid and excess hormone production. It can present with a toxic diffuse goitre. It is m ore common in women, with a female-to-male ratio of 7–8:1. The typical age range of presentation is 20 –40, but there have been reports in teenage patients. The patient in this scenario presents symptomatic of hyperthyroidism: nervousness, hypertension, diarrhoea and weight loss. Other symptoms include: sweating, heat intolerance, tachycardia, an increased appetite and emotional lability. This patient also exhibits signs of Graves’ ophthalmopathy with exophthalmos and proptosis from increased retro-orbital tissue. It is also associated with upper eyelid retraction and lid lag. Treatment of Graves’ disease involves antithyroid drugs such as carbimazole and propylthiouracil. Given the patient’s age propylthiouracil should be avoided due to the high risk of hepatotoxicity especially in the paediatric population. Other treatments involve radioactive iodine and thyroidectomy. Multiple endocrine neoplasia 2 (MEN type 2) Multiple endocrine neoplasia type 2 is associated with tumours of the endocrine system and typically involves phaeochromocytoma and medullary thyroid cancer. Type 2A also involves hyperparathyroidism, while those with type 2B may demonstrate a Marfanoid body habitus. Even though the patient exhibits some signs associated with phaeochromocytoma, it is very unlikely in this age group. Additionally, exophthalmos is mostly associated with Graves’ disease, making hyperthyroidism a more likely diagnosis. Phaeochromocytoma Even though the patient exhibits some signs associated with phaeochromocytoma (hypertension, weight loss, diarrhoea, anxiety), it is an unlikely diagnosis in this age group. Additionally, exophthalmos is mostly associated with Graves’ disease, making hyperthyroidism a more likely diagnosis. Retro-orbital pseudotumour A retro-orbital pseudotumour is an inflammatory condition involving the extraocular muscles that presents with painful unilateral exophthalmos and diplopia. It is not associated with diarrhoea or weight loss. Acute appendicitis Even though acute appendicitis can present with diarrhoea as well as hypertension and anxiety relating to pain, it is not associated with exophthalmos or weight loss as in the scenario above.

Answer 100

Explanation A phaeochromocytoma can be shown by metaiodobenzylguanidine (MIBG) scintigraphy MIBG scintigraphy is a very specific test for detecting phaeochromocytoma. Radioactive iodine-131-metaiodobenzylguanidine is administered to the patient and localises to adrenergic tissue. In the case of a patient with a phaeochromocytoma there is a focal area in the adrenal medulla where there is very strong and prolonged uptake of the solution. MIBG scintigraphy is not considered the first line investigation to detect phaeochromocytoma. MIBG is useful in detecting extra-adrenal tumours or disease recurrence. Renovascular disease is a rare cause of secondary hypertension Secondary hypertension accounts for 5–10% of hypertensive patients. Renovascular disease is the most common cause of secondary hypertension, occu rring due to narrowing of the renal artery (renal artery stenosis). It typically presents in young women (<30 years) and older men (>50 years). Other causes of secondary hypertension include: Conn syndrome, Cushing syndrome, phaeochromocytoma, hyperthyroid ism, congenital adrenal hyperplasia, use of oral contraceptives, and pregnancy. Most adrenal incidentalomas are hormone secreting Adrenal incidentalomas are described as adrenal masses found incidentally. Of these, 85% are non-functional, ie do not secrete any hormones and the remaining 15% are either hormone-secreting or malignant. A raised midnight cortisol is diagnostic of Cushing's syndrome Cortisol levels are secreted in a diurnal rhythm. They peak in the morning between 0700–0900 h and then gradually reduce throughout the day, reaching a nadir at around midnight. In Cushing syndrome there is loss of the diurnal rhythm and a raised midnight cortisol is thought to be the earliest sign of Cushing syndrome with a very high sensitivity. However, other factors can cause a midnight cortisol surge such as stress resulting from physical illness, being awake at midnight to perform the test and depression. As a result, for the diagnosis of Cushing syndrome the dexamethasone suppression test is used. 30% of phaeochromocytomas are extra-adrenal About 10% of phaechromocytomas are extra-adrenal. It is important to remember that phaeochromocytoma follows the rule of 10s: 10% are malignant, 10% are bilateral, 10% are found in children, 10% of patients have multiple tumours, 10% are extra -adrenal (found in the thorax, neck, bladder, kidney, scrotum) and 10% are familial (von Hippel –Lindau syndrome).

Answer 101

Explanation With antithyroid drugs patients have a high recurrence rate when therapy is discontinued Antithyroid drugs do not offer permanent control as seen with surgery or radio-iodine. If the patients discontinue their antithyroid medication, hyperthyroidism recurs in the vast majority of cases. Antithyroid medication such as propylthiouracil and carbimazole work as hormone antagonists therefore following cessation the disease can recur. Combining antithyroid medication and radio -iodine therapy increases the rate of achieving permanent control. Surgery is the most rapid method of permanent control and results in euthyroidism in about 50% of cases at 5 years Thyroid surgery can lead to hypothyroidism, and occurs in 90% of patients post - operatively at 5 years and this rises to almost 100% in 20 years. Surgery has no permanent complications Thyroid surgery is not without complications. These are grouped in to immediate, early and late complications. Radio-iodine therapy gives permanent control and has a low rate of hypothyroidism Radio-iodine therapy yields good results and generally has a lower rate of recurrence of hyperthyroidism when compared to medical therapy only. Return to a euthyroid state takes about 2 months following treatment. Hypothyroidism is however a common complication following radio-iodine therapy, affecting patients at a rate of up to 90% in the first year. All other treatments, except surgery, are contraindicated in pregnancy Hyperthyroidism in pregnancy affects about 0.2% of pregnancies with Graves’ disease being the most common cause, followed by gestational hyperthyroidism. During pregnancy, the treatment options for hyperthyroidism ar e limited to antithyroid medication and surgery. Radioactive iodine is contraindicated during pregnancy. During early pregnancy, propylthiouracil should be used, as carbimazole has a risk of teratogenic effects. After the first trimester, the use of carbim azole can resume for the remainder of the pregnancy, as propylthiouracil is associated with hepatotoxicity. Surgery in pregnancy is reserved for cases of malignant disease where there is uncontrolled hyperthyroidism or airway compromise. Otherwise, it is g enerally advised for the operation to be postponed until after delivery due to the risk of general anaesthesia on the fetus.

Answer 102

Explanation It may be screened for by urinary catecholamines Phaeochromocytoma is a rare neuroendocrine tumour, arising in the adre nals in 90% of the cases, producing an excess amount of catecholamines. In patients where a phaeochromocytoma is suspected, quantifying urinary total catecholamines and metanephrines in a 24-hour urine sample collection, has the highest sensitivity and specificity. Assessing the level of vanillylmandelic acid in a 24 -hour urine sample is not as accurate. It is usually bilateral Phaeochromocytoma follows the rule of 10s. Only 10% of cases are bilateral. It is usually extra-adrenal Phaeochromocytoma follows the rule of 10s. Only 10% of cases are extra-adrenal and have been described in the thorax, neck, bladder, kidney and scrotum. It is usually malignant Phaeochromocytoma follows the rule of 10s. Only 10% of cases are malignant. It is best treated medically There is no effective medical treatment for phaeochromocytoma. The patient is adequately prepared pre-operatively with a-blockers and then b-blockers before surgical removal of the phaeochromocytoma.

Answer 103

Explanation Conn syndrome The patient shows signs of Conn syndrome, with secondary hypertension, hypernatraemia, hypokalaemia and a metabolic alkalosis. Conn syndrome is primary hyperaldosteronism, ie excess secretion of aldosterone. Aldosterone is produced in the zona glomerulosa of the cortex of the adrenals. It is a mineralocorticoid hormone that acts on the mineralocorticoid receptors, found mainly in the distal convoluted tubule and collecting ducts of the nephron, activating the basolateral Na + /K + ion channels to reabsorb sodium and water and excrete potassium. It increases the permeability of the collecting duct to sodium and stimulates the secretion of H + ions into the urine. Through conservation of sodium and water, aldosterone increases blood pressure. In hyperaldosteronism, there is excessive release of aldosterone, typically from either adrenal hyperplasia or an adenoma. Conn syndrome most commonly affects women, with a female to male ratio of 2:1, aged 30–50. Presenting features of Conn syndrome include: hypertension, abdominal distension, weakness, ileus or features related to complications of hypertension such as headaches, proteinuria. Treatment incudes spironolactone (an aldosterone antagonist) or surgery with adrenalectomy. Addison’s disease Addison’s disease is the result of adrenocortical insufficiency and may present with hypotension. It is associated with biochemical disturbances which include hyponatraemia, hyperkalaemia and hypercalcaemia. Coarctation of the aorta Coarctation of the aorta is a known cause of secondary hypertension but does not lead to the biochemical disturbances evident in the above scenario. Incidental findings in patient with essential hypertension Essential hypertension does not have a known cause and should not be associated with biochemical abnormalities of hypernatraemia, hypokalaemia and metabolic alkalosis. Phaeochromocytoma Phaeochromocytoma is a known cause of secondary hypertension, but does not lead to the biochemical abnormalities evident in the scenario.

Answer 104

Explanation Small-cell bronchial carcinoma The patient presents with signs relating to Cushing syndrome, characterised by the excess production of cortisol in the body. The raised ACTH excludes an adrenal cause. The high-dose overnight dexamethasone suppression test is used to differentiate ACTH -dependent causes of Cushing syndrome. If the cause is a pituitar y adenoma then high-dose dexamethasone suppresses the production of ACTH from the adenoma cells and therefore causes a low morning cortisol. As the cortisol level remained unaffected, the source of ACTH is not the pituitary and is therefore an ectopic sour ce. From the options available, small-cell bronchial carcinoma, accounting for 15% of all primary lung tumours, is the most common cause of ectopic ACTH production. This is a paraneoplastic syndrome that can occur with the following tumours: small -cell lung tumours, bronchial carcinoid tumours, islet-cell tumours of the pancreas, medullary carcinoma of the thyroid and thymic tumours. Signs of Cushing syndrome are summarised in the table below: Head and neck Trunk Limbs Frontal balding Kyphosis Proximal myopathy Moon face Buffalo hump Pathological fractures Acne Gynaecomastia in men Ankle oedema (salt and water retention due to excess cortisol) Plethoric complexion Central obesity (due to altered fat distribution) Hirsutism Purple striae on abdomen, breasts, thighs Pigmentation in ACTH-dependent cases, in areas exposed to sunlight Thin skin Hair growth of forearms in particular Tissue wasting Predisposition to infection Bad wound healing Adrenocortical adenoma When Cushing syndrome is the result of an adrenal cause, such as an adrenocortical adenoma or an adrenocortical carcinoma, the excess circulating cortisol suppresses the hypothalamus–pituitary axis and leads to a low corticotrophin releasing hormone (CRH) and ACTH. In this scenario ACTH is high as is morning cortisol. Adrenocortical carcinoma Where Cushing syndrome is the result of an adrenal cause, such as an adrenocortical adenoma or an adrenocortical carcinoma, the excess circulating cortisol suppresses the hypothalamus–pituitary axis and leads to a low CRH and ACTH. In this scenario ACTH is high as is morning cortisol. Basophil pituitary adenoma Cushing’s disease is caused by a pituitary adenoma, arising in either the basophil or chromophobe cells. However, in this scenario the cause of the patient’s presentation is not a pituitary adenoma. In the case of a pituitary adenoma, cortisol level should be suppressed, following a high-dose overnight dexamethasone suppression test. Bronchial carcinoid Both bronchial carcinoid and small-cell bronchial carcinoma can produce a Cushing syndrome by ectopic secretion of ACTH. Small -cell bronchial carcinoma is more common that bronchial carcinoid. Bronchial carcinoid is a rare entity, accounting for 1–6% of primary lung tumours and tends to present between the 4th and 5th decade of life.

Answer 105

Explanation Phaeochromocytoma Phaeochromocytoma is found in patients with both MEN2A and MEN2B syndromes. Patients with MEN2A have the following combination of conditions: medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (parathyroid hyperplasia). MEN2 is an autosomal-dominant condition associated with the RET proto-oncogene. There is also a third variation of MEN2 called familial MEN2, presenting with a medullary thyroid carcinoma and no other manifestations. MEN2A (Sipple syndrome): type 2 = secondary = Sipple. Pituitary adenoma Pituitary adenomas are associated with multiple endocrine neoplasia type 1. This condition is described as the combination of: parathyroid hyperplasia, pancreatic islet - cell tumours and a pituitary adenoma. Gastrinoma A gastrinoma is a gastrin-secreting tumour most commonly found in the duodenum or pancreas and can lead to Zollinger–Ellison syndrome – peptic ulceration because of excess. Up to 50% of patients with Zollinger–Ellison syndrome are found to have MEN1. Marfanoid habitus Marfanoid habitus is seen in patients with multiple endocrine neoplasia type 2B. This condition describes the combination of medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas and Marfanoid body habitus. Neurofibromatosis Neurofibromatosis is not part of multiple endocrine neoplasia.

Answer 106

Explanation Hypermagnesaemia may be seen Familial hypocalciuric hypercalcaemia (FHH) is a rare autosomal -dominant condition with high penetrance, associated with loss-of-function mutations in the calcium sensing receptor (CaSR), a G-coupled protein receptor which is found in the kidney and parathyroid tissue. In the parathyroid gland its function is to sense serum calcium levels and regulate parathyroid hormone (PTH) release, whereas in the kidney it inhibits reabsorption of calcium. In FHH, there is loss of the negative feedback system on PTH release when serum calcium is elevated due to a reduction in the receptor’s sensitivity, leading to sustained mild hypercalcaemia. In the kidney there is reduced excretion leading to hypocalciuria. In most cases there is also hypermagn esaemia. Patients are usually asymptomatic. FHH is confirmed with genetic testing. It is autosomal-recessive Familial hypocalciuric hypercalcaemia is inherited in an autosomal -dominant fashion with a high penetrance. It is associated with increased urinary calcium excretion – more than 200 mg per 24 h Familial hypocalciuric hypercalcaemia is characterised by raised serum calcium levels, low urinary calcium levels, normal or slightly elevated parathyroid hormone level and commonly associated with hypermagnesaemia. It is associated with low parathyroid hormone (PTH) levels Familial hypocalciuric hypercalcaemia is characterised by normal or slightly raised levels of parathyroid hormone. The condition responds to parathyroidectomy In patients that are asymptomatic, treatment is not necessary. Familial hypocalciuric hypercalcaemia should not be treated with parathyroidectomy and does not respond to diuretic or bisphosphonate treatment. Calcimimetics have been used for symptomatic cases as well as pamidronate. Parathyroidectomy is reserved for patients with recurrent pancreatitis.

Answer 107

Explanation Cushing syndrome Cushing syndrome is a condition related to excess cortisol. The commonest cause is iatrogenic, resulting from exogenous administration of glucocorticoid medication for chronic conditions such as asthma, chronic obstructive pulmonary disease (COPD), arthritis etc. Endogenous causes of Cushing inclu de: a pituitary adenoma producing an excess of adrenocorticotropic hormone (ACTH), adrenocortical adenoma or carcinoma and a functional tumour producing ectopic adrenocorticotropic hormone (ACTH) such as an oat-cell lung carcinoma. Cushing syndrome relates to a collection of signs and symptoms that occur as the result of excess cortisol. These are summarised in the table below: Head and neck Trunk Limbs Frontal balding Kyphosis Proximal myopathy Moon face Buffalo hump Pathological features Acne Gynaecomastia in men Ankle oedema (salt and water retention due to excess cortisol) Plethoric complexion Central obesity (due to altered fat distribution) Hirsutism Purple striae on abdomen, breasts, thighs Pigmentation in ACTH-dependent cases, in areas exposed to sunlight Thin skin Hair growth of forearms in particular Tissue wasting Predisposition to infection Bad wound healing Addison’s disease Addison’s disease is the result of adrenocortical insufficiency and can present with hypotension. It is associated with biochemical disturbances as well: hyponatraemia, hyperkalaemia and hypercalcaemia. Congenital adrenal hyperplasia Congenital adrenal hyperplasia is an autosomal-recessive condition associated with deficiency in the enzyme 21α-hydroxylase, involved in the synthesis of cortisol and aldosterone. It tends to present at birth or early infancy. Conn syndrome Conn syndrome is a condition associated with hyperaldosteronism. It is mineralocorticoid and not glucocorticoid excess. Even though patients with Conn syndrome present with hypertension, the remaining signs described in the scenario above relate to glucocorticoid excess. Patients with Conn syndrome present with hypernatraemia and hypokalaemia. Phaeochromocytoma Phaeochromocytoma is a rare neuroendocrine tumour, arising in the chromaffin cells of the adrenals in 90% of the cases, producing an excess amount of catecholamines. Even though it is associated with hypertension, the remaining signs described in the scenario relate to corticosteroid excess. Patients with phaeochromocytoma present with severe hypertension associated with headaches, palpitations and diaphoresis.

Answer 108

Explanation Thyroid-stimulating hormone receptor immunoglobulins Graves’ disease is a form of hyperthyroidism of autoimmune origin. It is associated with the presence of circulating TSH receptor immunoglobulins (antibodies), that bind to the TSH receptor in the thyroid. These antibodies mimic the function of TSH, leading to stimulation of the thyroid gland to produce more triiodothyronine (T3) and thyroxine (T4). The elevated serum-circulating hormones activate the negative feedback mechanism and suppress release of TSH from the anterior pituitary gland. Low thyroxine; which regulates carbohydrate metabolism Thyroxine (T4) is the hormone produced from the thyroid gland. Graves’ disease is a state of hyperthyroidism. Therefore, serum thyroxine level s would be raised. Thyroxine stimulates lipid and carbohydrate metabolism. Raised thyroxine; secreted by the colloid cells of the thyroid gland Raised thyroxine is found in patients with Graves’ disease as this is a form of hyperthyroidism, however thyroxine is secreted by the follicular and not the colloid cells of the thyroid gland. Raised thyroxine level; mostly bound to albumin in the blood In overt hyperthyroidism there is a raised free (unbound) thyroxine level (free T4). Raised thyroxine-stimulating hormone (TSH) from the posterior pituitary TSH is secreted from the anterior pituitary. However, the cause of Graves’ disease is not raised TSH but the presence of TSH receptor immunoglobulins, that mimic the function of TSH by binding to the TSH receptor and stimulating the thyroid gland to release hormone molecules. TSH is suppressed via a negative feedback mechanism and is therefore low in patients with Graves’ disease.

Answer 109

Explanation The adenoma could be localised by a combination of ultrasound and sestamibi radionucleotide scan Pre-operative parathyroid adenoma localisation can be done by either ultrasound, sestamibi (methoxyisobutylisonitrile (MIBI), uses technetium) radionucleotide scan or technetium/thallium scan. The inferior parathyroids are much more variable in their position. This parathyroid gland would have developed from the second branchial pouch The superior and inferior parathyroids develop from the fourth and third branchial pouches, respectively. This would be an unusual case, as the majority o f primary hyperparathyroidism is due to diffuse hypertrophy of the parathyroids Primary hyperparathyroidism is usually due to a solitary secreting parathyroid adenoma. Hyperparathyroidism presents as:  ‘bones’ (arthralgia and osteoporosis)  ‘stones’ (renal)  abdominal ‘groans’ (pancreatitis, peptic ulcers and constipation)  ‘moans’ (depression, fatigue and weakness). This woman’s weakness and fatigue are incidental to the hypercalcaemia This woman’s weakness and fatigue are almost definitely as a result of her hypercalcaemia. Parathyroid tissue cannot be implanted elsewhere in the body after total parathyroid excision Tertiary hyperparathyroidism occurs in renal failure, in which the parathyroids function autonomously. In such cases, subcutaneous reimplantation of half a parathyroid in the forearm allows easy access if further resection is required.

Answer 110

Explanation Iatrogenic steroids This woman has Cushing syndrome and the commonest cause of this is iatrogenic through the administration of steroids. In this case, this woman has poorly controlled polymyalgia rheumatica (PMR) and is likely to have been on prolonged steroid treatment. Endogenous cases are caused by primar y pituitary disease ie pituitary adenoma (70%, referred to as Cushing's disease), primary adrenal tumours (15%) and ectopic adrenocorticotropic hormone (ACTH)-secreting tumours (15%). The diagnosis of Cushing syndrome depends on the loss of normal circadia n rhythm as well as persistent elevation of cortisol. It is necessary to take at least three serum samples to demonstrate the loss of rhythm. The mean 24 -h cortisol levels can be estimated by collecting and measuring the 24-h urinary free cortisol, which gives an integrated measure of cortisol production. As a screening test it has 95% specificity. Medullary carcinoma of the thyroid Medullary carcinomas of the thyroid can rarely produce ectopic adrenocorticotropic hormone (ACTH), however iatrogenic administration of steroids is more likely in this case given the history of PMR. Pituitary tumour Pituitary tumours can produce adrenocorticotropic hormone (ACTH), however, the history of polymyalgia rheumatica (PMR) means iatrogenic steroid administration is more likely. Lung tumour secreting adrenocorticotropic hormone (ACTH) ACTH secreting tumours, of which bronchial carcinoma is the most common, can cause Cushing syndrome, however there is no history indicative of lung cancer. Polymyalgia rheumatica Administration of steroids to treat polymyalgia rheumatica (PMR), not PMR per se, causes Cushing syndrome.

Answer 111

Explanation Only surgery is curative Parathyroidectomy is the only curative treatment for primary hyperparathyroidism caused by a parathyroid adenoma. Bisphosphonates and calcitonin result in good long-term control Bisphosphonates, calcitonin and octreotide do not have a role in treatment. Octreotide results in good control of parathyroid hormone (PTH) levels Octreotide is used in nuclear imaging. Parathyroid tumours expressing somato statin may show octreotide uptake, which may indicate a possibility for the use of somatostatin analogues for medical treatment when surgery is not possible. Octreotide does not have a role in the treatment of primary hyperparathyroidism. Surgery is reserved for those not improving on bisphosphonate treatment Surgery is the only curative treatment of primary hyperparathyroidism secondary to a parathyroid adenoma. Bisphosphonates do not have a role in treatment of primary hyperparathyroidism. Reducing dietary calcium intake can be curative Low calcium intake stimulates the parathyroids and high intake accentuates hypercalcaemia, so the recommendation is moderate intake followed up with curative surgery by removal of the parathyroid glands.

Answer 112

Explanation She will probably be asymptomatic Asymptomatic primary hyperparathyroidism is found in greater than 50 % of patients. In 85% of cases, it is caused by a single parathyroid adenoma, but can be due to multiple gland adenomas/hyperplasia and rarely even parathyroid carcinoma. She will also have diabetes mellitus Patients with primary hyperparathyroidism are very slightly more likely to also have diabetes and vice versa. It is not certain therefore that this patient would have diabetes. She will have reduced parathyroid hormone (PTH) levels Patients will have a raised serum calcium and parathyroid hormone and a reduced phosphate (secondary to renal excretion, causing phosphaturia). She will have a raised phosphate As mentioned, the patient will have a low phosphate due to renal excretion of phosphate in response to raised serum calcium and parathyroid hormone. She will have MEN2b syndrome Hyperparathyroidism is found in MEN 1 and MEN 2a syndromes, but not in MEN 2b.

Answer 113

Explanation Fine-needle aspiration cytology Thyroid nodules are common, and the majority are within multinodular goitres. The most useful initial investigations are ultrasound and fine-needle aspiration cytology of any dominant nodules. Thyroid function tests in patients with multinodular goitre or a solitary thyroid nodule are usually normal. These are therefore usually only necessary if you suspect a hot nodule in a symptomatic patient. Only around 10 –20% of cold nodules in adults and 50% in children are malignant. Computed tomography (CT) scan Further imaging is only necessary if you suspect a very large goitre causing tracheal compression or retrosternal extension. In such cases, CT scan of the neck and thorax is useful. MRI scan MRI scanning does not have a role in the investigation of a simple thyroid nodule. Technetium radio-isotope scan Technetium radio-isotope scan is useful for the assessment of parathyroid adenomas and the myocardium, but is not used in the assessment of thyroid nodules. Core biopsy Fine-needle aspiration, not core biopsy, is sufficient in gaining samples from nodules for histological examination. Furthermore, fine-needle aspiration is less invasive than core biopsy.

Answer 114

Explanation Multiple Endocrine Neoplasia IIA Multiple Endocrine Neoplasia II (MEN II) is an autosomal-dominant disorder caused by mutations in the RET proto-oncogene. MEN II has three distinct subtypes – MEN IIA, MEN IIB, and familial medullary thyroid carcinoma only. MEN IIA describes the association of medullary thyroid carcinoma, phaeochromocytomas and parathyroid tumours. Patients with pheochromocytomas may present with hypertension, tachycardia, sweating and headaches. Cutaneous lichen amyloidosis in patients with MEN IIA manifests as multiple pruritic scaly skin lesions in the scapular area of the back. Multiple Endocrine Neoplasia (MEN) I MEN I is characterised by carcinomas of the pituitary, pancreas and parathyroid. This patient has symptoms of a phaeochromocytoma, which is then confirmed on investigation. Phaeochromocytomas are not present in MEN I. Secondary hyperparathyroidism This is most commonly seen in patients with chronic kidney disease causing hypocalcaemia and hyperphosphataemia which then stimulates the parathyroid glands. Multiple Endocrine Neoplasia IIB MEN IIB can be distinguished from MEN IIA due to the presence of marfanoid features and mucosal neuromas, neither of which are described in the case history. In MEN IIB, the medullary cancer is very aggressive with most patients dying before developing either a phaeochromocytoma or hyperparathyroidism. Carcinoid tumour Carcinoid tumours most commonly secrete ectopic serotonin, excess levels of which would not produce the clinical picture described in the case history. Instead they are likely to present with flushing, diarrhoea, abdominal cramps and wheezing.

Answer 115

Explanation Papillary carcinoma Papillary carcinoma is the commonest malignant thyroid tumour. This is more common in younger patients, women and those with a past history of head and neck irradiation. It often spreads to local lymph nodes. Orphan Annie nuclei are characteristic, psammoma bodies may also be seen. It is extremely responsive to treatment and prognosis is excellent. Follicular adenoma Follicular adenomas of the thyroid are benign and therefore would not metastasise to the regional lymph nodes as described in the case history. Anaplastic carcinoma Anaplastic carcinoma is an extremely aggressive thyroid cancer and is usually unresponsive to treatment. It more commonly presents in elderly patients. Medullary carcinoma Medullary carcinoma only accounts for around 3% of thyroid cancer and therefore it is more likely the patient described has a papillary carcinoma. Follicular carcinoma Follicular carcinoma more commonly presents in women over the age of 50, accounts for around 15% of all thyroid cancer, and has a good prognosis.

Answer 116

Explanation Hypothyroidism due to a primary abnormality in the hypothalamus Tertiary hypothyroidism, also called hypothalamic -pituitary axis hypothyroidism, results when the hypothalamus fails to instruct the pituitary to produce sufficient TSH. This young woman’s hypothyroidism improves with TRH administration, confirming the diagnosis of tertiary hypothyroidism. Hyperthyroidism due to a thyroid tumour The patient has no signs or symptoms of thyroid malignancy, which often presents with a firm mass noticed by the patient which arises from the thyroid. Hyperthyroidism due to a primary abnormality in the hypothalamus The patient has symptoms of hypothyroidism, not hyperthyroidism. Hyperthyroidism can present with palpitations, tremor, weight loss (despite increased appetite), fatigue, hair loss and heat intolerance. Hypothyroidism due to a primary abnormality in the pituitary gland As her TSH level increases in response to TRH, this suggests there is no abnormality in the pituitary gland. Hypothyroidism due to a primary abnormality in the thyroid gland The administration of TRH and subsequent increase in TSH suggests that the primary abnormality is due to an abnormality with the hypothalamus.

Answer 117

Explanation Increased gastrin secretion Zollinger–Ellison syndrome is a result of an endocrine tumour of the pancreatic G -cells (gastrinoma) and results in gastrin hypersecretion with resultant severe gastric ulceration. The normal physiological stimulation of gastric secretion has three phases:  cephalic  gastric  intestinal. The cephalic phase is vagally mediated and stimulated by the sight and smell of food. The parasympathetic input causes gastrin release from antral G -cells, which causes acid and pepsin secretion. Vagal input also directly stimulates gastric glands and rel eases histamine from mast cells which activated parietal cells to produce acid. The gastric phase begins with food entering the stomach, distending it, causing vagal stimulation. This accounts for ~60% of gastric acid secretion. The intestinal phase only accounts for ~5% of secretion and gastrin secretion is mediated by the presence of food in the duodenum. Histamine antagonism Histamine agonism, not antagonism, would result in gastric hypersecretion. Somatostatin secretion Somatostatin is an inhibitory hormone and acts directly on parietal cells to reduce acid secretion. Vagal inhibition Vagal inhibition would reduce gastric secretion while ZE is characterised by severe gastric ulceration secondary to increased gastric secretion. Vagal stimulation The vagal nerve does play a role in the normal physiological stimulation of gastric secretion, most notably due to food entering the stomach causing vagal stimulation and subsequently gastric secretion. However, in ZE syndrome, excessive gastric secretion is due to increased gastrin secretion.

Answer 118

Explanation Flushing Carcinoid syndrome occurs secondary to carcinoid tumours which are neuroendocrine neoplasia. These tumours often secrete serotonin and can produce the following symptoms;  flushing  telangiectasia  diarrhoea  bronchospasm  right heart valve lesions (tricuspid regurgitation and stenosis, pulmonary stenosis)  pellagra (rarely). Alternating constipation Diarrhoea, not constipation, is associated with carcinoid syndrome. Dysmenorrhoea Dysmenorrhoea refers to pain during menstruation, and as the patient is male this is very unlikely indeed! Mitral regurgitation The tricuspid valve is more likely to be affected in carcinoid syndrome, and flushing is more likely than either of these. Nausea Nausea is a very non-specific symptom and is present in many conditions. Flushing is far more characteristic of carcinoid syndrome.

Answer 119

Explanation Zollinger–Ellison syndrome Zollinger–Ellison syndrome results from a gastrin-secreting tumour of the islet cells of the pancreas or rarely of the duodenum or gastric antrum. This causes an increase in the levels of circulating gastrin. It often presents as intractable duodenal ulceration with a high incidence of bleeding and perforation. If the ulcer perforates, the patient may present with the classical signs and symptoms of peritonitis. Approximately 25% of patients with Zollinger –Ellison syndrome are associated with multiple endocrine neoplasia type 1, with an associated adenoma of the parathyroid in approximately 25% of patients and hyperplasia of the adrenal and thyroid in 10% of patients. Proton pump inhibitors that suppress acid production and promote healing comprise first-line treatment. H-2 antagonists may also be used, but are less effective than proton pump inhibitors in reducing acid production. Surgery to remove the tumour is only undertaken if the ulcers are resistant to the above medical treatment options. Multiple endocrine neoplasia type I MEN I can be associated with Zollinger–Ellison syndrome in around 25% of patients, however there are no other features of MEN I, for example, hyperparathyroidism. Multiple endocrine neoplasia type IIa MEN II is characterised by parathyroid hyperplasia, medullary thyroid carcinoma and phaeochromocytoma. This condition would not cause raised gastrin levels or persistent gastric ulceration. Multiple endocrine neoplasia type IIb Again, MEN II would not cause persistent ulceration. MEN IIb is differentiat ed from MEN IIa by the presence of mucosal neuromas. None of the above The patient’s ulceration has not improved despite appropriate therapy, and he has been subsequently found to have raised gastrin levels, which is indicative of Zollinger–Ellison syndrome.

Answer 120

Explanation Gitelman’s syndrome Gitelman’s syndrome can be either autosomal recessive or dominant and is characterised by hypokalaemic metabolic alkalosis and with hypocalciuria and hypomagnesaemia. Blood pressure is low or normal. Liddle syndrome Causes of hypokalaemia with hypertension (potassium excretion usually >30 mmol/day) and low plasma renin activity include Liddle’s syndrome, which is an autosomal-dominantsyndrome of hypertension and variable degrees of hypokalaemic metabolic alkalosis. Cushing’s syndrome In Cushing’s syndrome (sustained overproduction of cortisol) patients will exhibit hypertension and low plasma renin activity. Liquorice excess With liquorice excess, 11-β-hydroxysteroid dehydrogenase metabolises co rtisol and prevents it from binding to the mineralocorticoid receptor. Acquired or congenital conditions in which this enzyme is inhibited have a Conn’s phenotype and this includes patients taking liquorice in excess and renovascular disease. Renovascular disease As mentioned, patients with acquired or congenital conditions in which 11-β- hydroxysteroid dehydrogenase is inhibited have a Conn’s phenotype and this includes patients taking liquorice in excess and with renovascular disease.

Answer 121

Explanation Plasma HbA1c >6.5% The 2011 WHO recommendations for diagnosis of type II diabetes mellitus suggests that Hb A 1c can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria al igned to the international reference values, and there are no conditions present that preclude its accurate measurement. An Hb A 1c of 48 mmol/mol (6.5%) is recommended as the cut point for diagnosing diabetes. A value of less than 48 mmol/mol (6.5%) does not exclude diabetes diagnosed using glucose tests. Situations when Hb A 1c is not appropriate for diagnosis of diabetes include:  children and young people  patients suspected of having type 1 diabetes  pregnancy  patients with symptoms of diabetes for less tha n 2 months  patients at high diabetes risk who are acutely ill  patients taking medication that may cause rapid glucose rise, eg steroids, antipsychotics  patients with acute pancreatic damage, including pancreatic surgery  presence of other factors that influence HbA 1c and its measurement (such as haemoglobinopathies, haemolytic disorders, alcohol excess or chronic kidney disease). Fasting plasma glucose >6.0 mmol/l Diabetes may be diagnosed with a fasting plasma glucose >7.0 mmol/l and associated diabetic symptoms such as increased thirst/urination, recurrent infections or weight loss. It must be remembered, however, that compliance with the fasting period is often poor. Random plasma glucose >12.0 mmol/l A random plasma glucose of >11.1 mmol/l is sufficient for the diagnosis of diabetes. Again, symptoms of diabetes must be present. Plasma glucose <7.8 mmol/l at 2 h after glucose-tolerance test The glucose-tolerance test can be used to diagnose diabetes. Here, 75 g of glucose is administered to the patient and if their venous glucose is > 11.1 mmol/l at 2 h following administration then diabetes can be diagnosed. Glucose-tolerance test is required for confirmation of diagnosis The glucose-tolerance test is only one of the several available diagnostic tests that can be utilised.

Answer 122

Explanation Ectopic ACTH-secreting tumour A raised ACTH level with a raised cortisol implies that the problem is caused by excess ACTH production, otherwise negative feedback would suppress ACTH. Although failure of cortisol suppression after low-dose dexamethasone may be seen with both pituitary tumours (ieCushing’s disease) and ectopic ACTH-secreting tumours, high-dose dexamethasone often results in cortisol suppression for pituitary tumours, as they retain a degree of negative feedback. A persistently raised cortisol level after high-dose dexamethasone suppression therefore implies that an ectopic ACTH-secreting tumour is the most likely pathology. Adrenal tumour An adrenal adenoma can produce excess cortisol, however this would have the effect of suppressing ACTH production due to a negative feedback loop. Carney syndrome Carney syndrome comprises atrial myxoma and freckles with high cortisol leve ls independent of ACTH. Cushing’s disease Cushing’s disease refers to a pituitary adenoma that secretes excess ACTH. Given that the morning cortisol level remains high despite the high-dose dexamethasone suppression test suggests there is ectopic ACTH production, as even pituitary tumours retain some negative feedback. Depression Depression does not result in persistently raised cortisol and ACTH levels.

Answer 123

Explanation Squamous-cell carcinoma of the bronchus Hypercalcaemia is a frequent complication of cancer, and is most usually the result of the secretion of parathyroid hormone-related peptide (paraneoplastic syndrome). Squamous-cell carcinomas are particularly frequently responsible, but hypercalcaemia is uncommon with other bronchogenic cancers. Carcinoid tumours Carcinoid tumours sometimes secrete vasopressin or adrenocorticotrophic hormone (ACTH), but rarely cause hypercalcaemia. Lymphoma In lymphomas, unregulated extrarenal production of calcitriol can be responsible. Multiple myeloma In myeloma, the secretion of osteoclast-activating cytokines is the usual cause of hypercalcaemia. Small-cell carcinoma of the bronchus Small-cell carcinoma of the bronchus is more commonly associated with ectopic ACTH and antidiuretic hormone (ADH) secretion [the latter leading to syndrome of inappropriate antidiuretic hormone secretion (SIADH)], as well as Lambert–Eaton myasthenic syndrome.

Answer 124

Explanation Hilar lymphadenopathy The presence of hilar lymphadenopathy in a patient (especially an Afro-Caribbean patient) with hypercalcaemia should raise a suspicion that the latter is due to sarcoid (in which the granulomas secrete calcitriol, 1,25 -dihydroxycholecalciferol). Bone pain Bone pain can occur with hypercalcaemia secondary t o malignancy or hyperparathyroidism. Polyuria Polyuria is a feature of severe hypercalcaemia, irrespective of the cause. Short QT interval A short QT interval is also a non-specific feature of hypercalcaemia. Ureteric colic Ureteric colic is particularly associated with primary hyperparathyroidism, but is not specific to this cause.

Answer 125

**Correct Answer:** **1) A hypothalamic disorder** --- **Explanation:** - The patient has **hypogonadotropic hypogonadism** (low LH, FSH, and testosterone), which suggests a problem with the hypothalamus or pituitary gland. - The **subnormal response to a single GnRH injection** but **normal response after 7 days of GnRH stimulation** indicates that the pituitary gland is intact but not receiving sufficient GnRH from the hypothalamus. This pattern is characteristic of a **hypothalamic disorder**, such as **Kallmann syndrome** (a congenital GnRH deficiency). - A pituitary disorder would typically show no response to GnRH stimulation, even after repeated doses. - Klinefelter’s syndrome, mumps orchitis, and seminiferous tubular dysfunction are associated with primary hypogonadism (high LH and FSH with low testosterone), which is not seen in this case. This question tests the candidate's ability to interpret endocrine test results and understand the pathophysiology of delayed puberty.

Answer 126

Explanation Papillary thyroid carcinoma Papillary carcinoma of the thyroid gland accounts for around two-thirds of thyroid malignancies. The tumour spreads via the lymphatics and at presentation over half of patients will have cervical lymph node involvement. Histologically psammoma bodies are typical. Anaplastic thyroid carcinoma Anaplastic carcinoma is a very aggressive tumour type that is most commonly found in the elderly. It has a very poor prognosis with few patients surviving beyond 1 year. Follicular thyroid carcinoma Follicular thyroid carcinoma accounts for 20% of thyroid tumours and classically spreads via the bloodstream. Therefore lymph node involvement at presentation is very uncommon. Lymphoma Thyroid lymphoma is very rare affecting predominantly women over the age of 70 years, many of whom have a diagnosis of Hashimoto’s thyroiditis. Medullary thyroid carcinoma Medullary thyroid carcinoma occurs in 5 –10% of thyroid malignancies. It is derived from C-cells and therefore produces calcitonin, which can be measured in the blood.

Answer 127

Explanation Insulinoma Insulinomas are not common and occur in around 1 in a million of the population. They arise from β islet cells and are mostly benign. They often cause symptoms relating to hypoglycaemia, eg light-headedness, mood swings and in some cases unconsciousness. The diagnosis should be suspected when Whipple’s triad is present – attacks brought on by fasting, hypoglycaemia (<2.0 mmol/l) during an episode and symptoms then improving with glucose administration. Gastrinoma A gastronome is a tumour found in the pancreas or duodenum that secretes gastrin. It is the most common cause of Zollinger–Ellison syndrome. Glucagonoma A glucagonoma is a rare tumour of the alpha cells within the pancreas causing excess levels of glucagon resulting in a high plasma glucose. Phaeochromocytoma Phaeochromocytoma is a neuroendocrine tumour of the adrenal gland that secretes excess catecholamines. Zollinger-Ellison syndrome Zollinger–Ellison syndrome is characterised by severe gastric ulceration secondary to tumour secreting gastrin.

Answer 128

Explanation Glucagonoma Glucagonomas are very rare tumours with an incidence of around 1 in 20 million. There are often metastases present when the patient presents. Classic features of glucagonomas are migratory necrolytic erythema (bright red, papular and blister-type rash that can affect any part of the body, especially around the mouth), diabetes mellitus and weight loss (somewhat paradoxical). The rash is very characteristic and may be sufficient evidence to raise the concern itself. It is secondary to a zinc deficiency in the skin. Cushing’s syndrome Cushing’s syndrome refers to prolonged exposure to cortisol and has several aetiologies, including iatrogenic steroid administration and pituitary tumours. Weight gain, not weight loss, is associated with Cushing’s syndrome. Skin changes, such as abdominal striae, may be apparent. Gastrinoma A gastrinoma is a tumour found in the pancreas or duodenum that secretes gastrin. It is the most common cause of Zollinger–Ellison syndrome. Insulinoma Insulinomas are not common and occur in around 1 in a million of the population. They arise from β islet cells and are mostly benign. They often cause symptoms relating to hypoglycaemia, eg light-headedness, mood swings and in some cases unconsciousness. The diagnosis should be suspected when Whipple’s triad is present – attacks brought on by fasting, hypoglycaemia (<2.0 mmol/l) during an episode and symptoms then improving with glucose administration. Phaeochromocytoma Phaeochromocytoma is a neuroendocrine tumour of the adrenal gland that secretes excess catecholamines.

Answer 129

Explanation Phaeochromocytoma Phaeochromocytomas are rare catecholamine-producing tumours that arise from sympathetic paraganglia cells that are collections of adrenaline-secreting chromaffin cells. They occur in around one in a million people and are the underlying cause for less than 1% of hypertension. Around 10% are bilateral, 10% are malignant, 10% are familial and 10% are extra-adrenal (the ‘rule of 10s’). The most common extra-adrenal site is the organ of Zuckerkandl, which is by the aortic bifurcation. The most common symptom is sweating, and other symptoms include paroxysmal headaches, palpitations and precordial pain. Pre-operative management with Alpha- and Beta- blockers is crucial before anaesthetic induction to minimise morbidity and mortality. Cushing syndrome Cushing syndrome refers to prolonged exposure to cortisol and has several aetiologies, including iatrogenic steroid administration and pituitary tumours. While it cause hypertension, headaches, palpitations and hyperhidrosis are not recognised symptoms of Cushing syndrome. Gastrinoma A gastrinoma is a tumour found in the pancreas or duodenum that secretes gastrin. It is the most common cause of Zollinger–Ellison syndrome. Neuroblastoma Neuroblastoma is a malignant tumour of nerve cells and can commonly arise in the adrenal glands, spinal cord and brain, however it would not account for the symptoms and signs described in the case history. Zollinger-Ellison syndrome Zollinger–Ellison syndrome is characterised by severe or recurrent peptic ulcerationsecondary to a gastrin-secreting tumour

Answer 130

Explanation Diabetes insipidus Diabetes insipidus (DI) is an uncommon condition with excessive production of urine and thirst. It is classified according to the source of the problem as cranial DI [deficiency in antidiuretic hormone (ADH) production] or nephrogenic DI (renal tubules unresponsive to ADH). The urine has a low specific gravity and osmolality. Glucagonoma A glucagonoma is a rare tumour of the alpha cells within the pancreas, causing excess levels of glucagon resulting in a high plasma glucose. Insulinoma Insulinomas are not common and occur in around one in a million of the population. They arise from β islet cells and are mostly benign. They often cause symptoms relating to hypoglycaemia, eg light-headedness, mood swings and in some cases unconsciousness. Type 1 diabetes mellitus As the random and fasting glucose levels are within the normal range, this makes a diagnosis of diabetes mellitus (DM) less likely Furthermore, type 1 DM is often diagnosed at an earlier age than this patient. Type 2 diabetes mellitus Again, as the plasma glucose levels are normal, this makes a diagnosis of diabetes mellitus less likely.

Answer 131

Explanation Vasopressin The pituitary gland is divided into two parts - the anterior pituitary gland (adenohypophysis) and posterior (neurohypophysis). These have different embryological origins and different functions. The neurohypophysis (posterior pituitary) secretes oxytocin and vasopressin (ADH). Follicle-stimulating hormone (FSH) The adenohypophysis produces gonadotrophins (LH and FSH), growth hormone, prolactin, thyroid-stimulating hormone and adrenocorticotrophic hormone (ACTH). Growth hormone The anterior pituitary produces growth hormone. Prolactin Prolactin is produced by the anterior pituitary. Thyroid-stimulating hormone The anterior pituitary produces thyroid -stimulating hormone (TSH).

Answer 132

Explanation Iodine deficiency Iodine deficiency can cause a goitre and is still found in mountainous areas, for example the Alps, Himalayas, and Andes. The thyroid function may be euthyroid or hypothyroid depending on the severity of the iodine deficiency. Iodine deficiency causes a generalised hyperplasia of the thyroid gland resulting in a large goitre (the so-called endemic goitre). Autoimmune hypothyroidism Autoimmune thyroiditis can present with a goitre and the patient may be either hyper - or hypothyroid. There is a familial element to autoimmune hypothyroidism, and it can also occur in the context of high iodine consumption. Hashimoto’s thyroiditis Hashimoto’s thyroiditis is an autoimmune condition that leads to gradual destruction of the thyroid gland resulting in hypothyroidism and a large painless goitre. Myxoedema coma This occurs in the context of severe hypothyroidism – the patients in this case history are euthyroid. Toxic multinodular goitre A toxic multinodular goitre is a common cause of hyperthyroidism, second only to Grave’s disease.

Answer 133

Explanation Oral glucose-tolerance test with GH levels In normal subjects an oral glucose-tolerance test will suppress GH to <2 mU/l, in patients with acromegaly, it is not suppressed, and increases in 50%. Growth hormone (GH) levels Serum GH levels are often elevated, but levels can fluctuate and a normal level does notexclude a diagnosis. Insulin-like growth factor-1 (IGF-1) levels IGF-1 levels are often raised with acromegaly. Prolactin levels Prolactin levels are raised in 30% of patients, but again does not confirm the diagnosis. Visual field testing Although visual field defects are common, this does not confirm the diagnosis.

Answer 134

Explanation Pituitary disease Most patients with pituitary-dependent Cushing’s syndrome, ie Cushing’s disease will suppress plasma cortisol following a high -dose dexamethasone test as illustrated in this case. Adrenal adenoma Adrenal adenomas may produce cortisol, however this would result in suppression of adrenocorticotrophic hormone (ACTH) due to the negative feedback loop to the pituitary. Adrenal carcinoma Adrenal carcinoma are extremely rare and may produce cortisol, although again this would result in suppression of ACTH. Ectopic ACTH A failure to suppress ACTH would suggest an ectopic source of ACTH or an adrenal tumour. Iatrogenic cause Although the most common cause for Cushing’s syndrome is exogenous steroid administration, this would have been excluded in the history for this patient.

Answer 135

Explanation Nelson’s syndrome Nelson’s syndrome involves a combination of skin hyperpigmentation and an expanding pituitary tumour. It mostly occurs following an adrenalectomy for Cushing’s disease and is caused by the reduction in circulating cortisol causing reduced negative feedback on the pituitary gland, and therefore and increased ACTH production. This increase in ACTH levels causes hyperpigmentation as it is physically related to and resembles melanocyte-stimulating hormone (MSH). Acromegaly Acromegaly is a disorder, often of the pituitary gland, resulting in excess production of growth hormone. It can present with visual field defects, however, given the history of the adrenalectomy, Nelson syndrome is more likely. Addison’s disease Addison’s disease is an autoimmune disorder resulting in primary adrenal insufficiency. Diabetes insipidus Diabetes insipidus is a condition whereby either the kidneys are not responsive to antidiuretic hormone (ADH) or there is a deficiency in production of ADH. This patient does not have excess thirst and micturition. Furthermore, visual field defects would not be expected. Waterhouse–Friderichsen syndrome This syndrome refers to haemorrhage within the adrenal glands, most commonly secondary to Neisseria meningitidis infection. These patients are often desperately unwell with overwhelming sepsis, for example as seen with meningitis.

Answer 136

Explanation 21-Hydroxylase The most common cause for CAH is an enzyme deficiency of 21 -hydroxylase (in 90% of cases). This is essential in cortisol synthesis, and reduced cortisol levels cause an increase in ACTH which results in increased precursors of cortisol which are instead switched to testosterone production. In women this can manifest as pseudohermaphroditism and in males as precocious sexual maturity. 3ß-hydroxysteroid dehydrogenase This enzyme has a role in the production of progesterone and therefore is not implicated in CAH. 11β-Hydroxylase This enzyme is involved in the final steps of synthesis of cortisol. Deficiencies can cause CAH, however it is less common than 21-hydroxylase. 11α-Hydroxylase This enzyme is involved in the hydroxylation of steroids such as cortisol and does not result in CAH. 17-Hydroxylase Deficiency in this hormone can result in CAH, however it is uncommon.

Answer 137

Explanation Graves’ disease Thyrotoxicosis affects almost 2% of the population and in 95% of cases is the result of one of three causes: Graves’ disease, multinodular toxic goitre and a toxic solitary nodule. The commonest of these is Graves’ disease, which is most common in women between 20 and 40 years. Grave’s disease is also associated with eye changes (exophthalmos, ophthalmoplegia) and pretibial myxoedema, in addition to the other signs and symptoms of hyperthyroidism. Congenital Congenital abnormalities can affect the thyroid gland, however this is more commonly hypothyroidism and would present at birth or shortly after. Multinodular toxic goitre Multinodular toxic goitre can cause thyrotoxicosis, however Graves’ disease is a more common cause. Riedel’s thyroiditis Riedel’s thyroiditis (woody hard thyroid) is rare and results in painless, chronic fibrosis of the thyroid gland. Some patients can become hypothyroid, however, very few become hyperthyroid. Toxic solitary nodule Again, a toxic solitary nodule may cause thyrotoxicosis, however it is much less common than either Graves’ disease or multi nodular toxic goitre.

Answer 138

Explanation 1% Primary hyperparathyroidism is caused by a solitary adenoma in 85 –90% of patients, hyperplasia in around 15–10% and a carcinoma in less than 1%. It may be diagnosed through routine blood tests on asymptomatic patients who are noted to have hypercalcaemia, or patients may develop symptoms. These symptoms mostly affect the kidneys and bone, and include nephrocalcinosis and renal calculi, and demineralisation of bone. 5% Parathyroid carcinoma is rare and causes primary hyperparathyroidism and is the underlying pathology in less than 1% of cases. Typically, the serum PTH concentration is extremely high, unlike for a parathyroid adenoma or hyperplasia, in which the PTH concentration is increased, but not massively. 10% Parathyroid carcinomas are rare, accounting for less than 1% of cases of primary hyperparathyroidism. Parathyroid gland hyperplasia, however, accounts for 10–15% of cases of hypercalcaemia with raised PTH levels. 30% Parathyroid carcinomas are rare, accounting for less than 1% of cases of primary hyperparathyroidism. 50% Parathyroid adenomas are the most common cause for primary hyperparathyroid ism. Parathyroid carcinomas are rare.

Answer 139

Explanation Tertiary hyperparathyroidism Tertiary hyperparathyroidism develops when the excessive PTH secretion in secondary hyperparathyroidism (eg due to chronic hypocalcaemia in renal failure) becomes autonomous. This often occurs when the underlying cause for chronic hypocalcaemia is corrected, eg following a renal transplant. Management options for tertiary hyperparathyroidism include total parathyroidectomy, subtotal parathyroidectom y or autotransplantation of parathyroid tissue into an arm muscle (where it can be easily located if problems persist). Patients require calcium and vitamin D replacement to correct bone disease and reduce the risk of recurrence. Hypoparathyroidism Hypoparathyroidism would present with low levels of PTH. Primary hyperparathyroidism Primary hyperparathyroidism is usually as a result of parathyroid adenomas. Given the history of chronic kidney disease and subsequent hyperparathyroidism, tertiary hyperparathyroidism is the likely cause. Pseudohypoparathyroidism This is an extremely rare condition in which there is resistance to PTH, resulting in hypocalcaemia and appropriately high PTH levels. Given the history of renal transplant and rarity of pseudohypoparathyroidism, tertiary hyperparathyroidism is more likely. Secondary hyperparathyroidism Secondary hyperparathyroidism occurs in the context of chronic kidney disease resulting in hypocalcaemia, this stimulates the parathyroid glands to increase production of PTH.

Answer 140

Explanation Follicular carcinoma cannot be diagnosed on fine-needle aspiration (FNA) Follicular carcinoma cannot be differentiated from follicular adenoma by FNA. Anaplastic cancer has a good prognosis Anaplastic cancer has a very poor prognosis, and is usually seen in older patients. Anaplastic cancer is commoner in younger patients As mentioned, it is more commonly in the elderly, particularly women over the age of 70 years. Follicular carcinoma is the most common type Papillary adenocarcinoma is the commonest type (70%). Female to male ratio for thyroid cancer is 3:1. Medullary cancer only occurs in patients with multiple endocrine neoplasia type II (MEN II) Medullary cancer of the thyroid is associated with the MEN II syndrome but most patients who have medullary cancer will not have MEN.

Answer 141

Explanation Lundh meal The Lundh meal is a combination of skimmed milk powder mixed with corn oil and dextrose used to assess exocrine pancreatic function. Following administration, serum lipase measurements can provide a good indicator of exocrine pancreatic status. The faecal elastase test is increasingly used for detecting exocrine insufficiency and is more acceptable to patients. Albumin levels Serum albumin level may be decreased for many reasons eg inadequate diet, sepsis, nephrotic syndrome. It is more commonly used to assess the synthetic function of the liver. Barium meal A barium meal will not provide a functional assessment of the exocrine status of the pancreas. CT While CT can be very good for imaging the pancreas and assessing anatomical abnormalities and gland atrophy, it does not provide any information about the exocrine status of the pancreas. Ultrasound Again, ultrasound imaging will not provide a function assessment of the exocrine function of the pancreas.

Answer 142

Explanation Blood tests show a high serum gastrin level This patient has Zollinger–Ellison syndrome. This syndrome is rare and can be linked with MEN type 1. It is characterised by high serum gastrin levels as a result of a gastrin - secreting neuroendocrine tumour usually situated in the pancreas. Treatment involves proton pump inhibitors and surgical excision of tumour or chemotherapy. Family history is unlikely to be relevant Family history is important when considering MEN syndrome, which is associated with Zollinger–Ellison syndrome. No further tests are required The patient has gastric erosions at a young age and warrants further investigation, particularly in light of the family history of MEN syndrome. Proton pump inhibitors are the mainstay of management Proton pump inhibitors are an important aspect of treatment in Zollinger– Ellison syndrome, however, the patient is likely to require surgical excision of the tumour or chemotherapy. The aetiology is likely to be alcohol related Alcohol can increase the risk of gastritis and associated erosions, and while medical students often have a high alcohol consumption there is no mention of excessive alcohol intake in this case history.

Answer 143

The most likely diagnosis for the 27-year-old woman presenting with these symptoms is **1) De Quervain’s thyroiditis**. Here are the key points supporting this diagnosis: - **Neck Pain and Radiating Symptoms**: The patient reports pain in the front of her neck that radiates to her jaw and ears, which is characteristic of De Quervain’s thyroiditis. - **General Malaise and Lethargy**: She has been feeling run down and lethargic, which aligns with the systemic symptoms often associated with De Quervain’s thyroiditis, such as myalgia, malaise, and fatigue. - **Thyroid Swelling and Pain**: The slight swelling in the anterior neck that exacerbates her pain on swallowing is consistent with De Quervain’s thyroiditis, which typically presents with a tender and swollen thyroid gland. - **Elevated T4 and T3 Levels**: The blood tests showing slightly elevated T4 and T3 levels are indicative of the initial hyperthyroid phase seen in De Quervain’s thyroiditis. These features collectively point towards De Quervain’s thyroiditis as the most likely diagnosis.

Answer 144

Explanation Hashimoto’s thyroiditis The condition associated with antithyroid microsomal antibodies (antithyroid peroxidase antibodies) and antithyroglobulin antibodies, presenting with a complaint of tiredness is Hashimoto’s thyroiditis. Hashimoto’s thyroiditis is an autoimmune thyroid condition, in which the presence of autoantibodies leads to cell d estruction in the thyroid, reduced hormone output and hypothyroidism. It is the most common cause of hypothyroidism in areas where there is adequate iodine intake. It is 10 times more common in women and tends to present in the ages of 30 –50, however it can present at any point during a patient’s lifetime. Hashimoto’s thyroiditis is associated with other autoimmune conditions such as pernicious anaemia and coeliac disease. It also increases the risk of developing lymphoma of the thyroid at a later stage in life. Patients tend to present with symptoms as described in the mnemonic below, of insidious onset, gradually worsening and the presence of a diffuse goitre. Treatment is with thyroid hormone supplementation. Surgery is not usually required unless there a re compression symptoms from the goitre. Administration of steroids can assist in the shrinking of the goitre pre-operatively. Hypothyroidism is 10 times more common in women than men and occurs mainly in middle life. Reidel’s thyroiditis Riedel’s thyroiditis is a rare condition. It describes the chronic fibrosis of the thyroid gland resulting in a rapidly growing, painful, hard and fixed thyroid mass. Fibrosis can extend outside the thyroid gland to surrounding structures. Grave’s disease Grave’s disease presents is a form of hyperthyroidism, commonly presenting with a toxic goitre. It is associated with the presence of IgG thyroid -stimulating immunoglobulins, that bind to the thyroid-stimulating hormone receptors and stimulate the production of thyroid hormones. Hypoparathyroidism Hypoparathyroidism is most commonly secondary to total thyroidectomy. It can also be idiopathic or due to inability of the bones or kidneys to respond to parathyroid hormone. In any case, it is not characterised by the presence of autoantibodies. Patients present with symptoms relating to hypocalcaemia such as paraesthesia in the extremities and peri-orally (circumoral), abdominal cramps and tetany. Idiopathic hypothyroidism The term idiopathic is used to describe disease where the cause is unknown therefore it does not apply in this case.

Answer 145

Explanation Papillary Papillary carcinoma is the most common thyroid carcinoma, accounting for about 80% of thyroid malignancies. It is a well-differentiated tumour, most commonly presenting in women aged 35–40. It can be familial and is associated with exposure to radiation, most significantly if this occurred in childhood. It most commonly presents as a solitary thyroid nodule that radiologically appears as a mass with irregular borders and is non-capsulated. It metastasises to the cervical lymph nodes and rarely to the lungs. Treatment is with surgical thyroidectomy ± regional lymph node clearance and radioactive iodine administration for positive lymph nodes. If the tumour is confined to the thyroid gland on diagnosis, it has an excellent prognosis and a 5-year survival rate of 95%. Anaplastic Anaplastic thyroid carcinoma is rare (1% of all thyroid malignancies), is highly malignant and has a very poor prognosis. Follicular Follicular carcinoma is the second most common type of thyroid malignancies and is more common in areas where there is a higher incidence of iodine deficiency. Lymphoma Primary thyroid lymphoma is a non-Hodgkin’s B-cell lymphoma associated with Hashimoto’s thyroiditis. Medullary Medullary thyroid carcinoma accounts for about 5% of all thyroid malignancies an d is associated with multiple endocrine neoplasia type 2.

Answer 146

Explanation Parathyroid adenoma The patient has hypercalcaemia and hypophosphataemia, pointing towards the diagnosis of primary parathyroid disease. This patient most likely has primary hyperparathyroidism, the most common cause of which is a single parathyroid adenoma (85%). Other causes include: parathyroid gland hyper plasia affecting all four parathyroid glands (10–15%), multiple parathyroid adenomas (3–5%) or a parathyroid carcinoma (1%). The adenoma produces an excess of parathyroid hormone leading to: excessive calcium resorption from bone, increased renal calcium reabsorption, increased renal phosphate excretion and increased production of 1,25-dihydroxyvitamin D3 . Therefore, blood tests reveal: a raised PTH, hypercalcaemia, hypophosphataemia and a raised vitamin D3 . Treatment of a parathyroid adenoma is by surgical removal of the parathyroid glands. For patients not fit/suitable for parathyroidectomy options for treatment include: preventing vitamin D deficiency, bisphosphonates to protect the bones, calcimimetics to control hypercalcaemia if required. Chronic renal failure Chronic kidney failure leads to secondary hyperparathyroidism. The diseased kidney fails to convert an adequate level of vitamin D to its active form, which reduces the amount of calcium absorbed from the intestines, and fails to excrete phosphate leading to formation of calcium phosphate compounds in the circulation and a reduction in free circulating calcium. Therefore, in secondary hyperparathyroidism there is a low serum concentration of calcium and vitamin D, a high serum concentration of para thyroid hormone and a high serum phosphate. Metastatic carcinoma The two most common causes of hypercalcaemia are primary hyperparathyroidism and hypercalcaemia of malignancy. The two are generally quite difficult to differentiate. In both calcium is raised (with hypercalcaemia of malignancy causing a more dramatic hypercalcaemia) and phosphate is low. parathyroid hormone (PTH) in primary hyperparathyroidism is raised whereas in hypercalcaemia of malignancy it can be low/normal/raised depending on the mechanism involved. Given the patient’s age and the fact that the symptoms have been ongoing for several months make parathyroid adenoma a far more likely diagnosis than metastatic carcinoma. The most common cancers associated with hypercalcaemia are: breast, l ung and myeloma. Pituitary adenoma A pituitary adenoma causes visual symptoms (bitemporal hemianopia), headaches and symptoms relating to the cellular origin of the adenoma. It does not commonly cause hypercalcaemia. Thyroid carcinoma Thyroid carcinoma can lead to hypercalcaemia, but this is usually seen with advanced disease.

Answer 147

Diagnosis of the 3-Week-Old Boy with Symptoms To determine the most likely diagnosis for the 3-week-old boy presenting with non-bilious vomiting, hypochloraemic metabolic alkalosis, hypokalaemia, and an epigastric mass, we need to analyze each symptom and correlate it with the potential diagnoses provided. Symptom Analysis Non-bilious vomiting: This type of vomiting is often associated with conditions affecting gastric outflow. In infants, this can indicate a blockage or narrowing in the pylorus (the opening from the stomach to the small intestine). Hypochloraemic metabolic alkalosis: This condition arises when there is a loss of hydrochloric acid (HCl) from the stomach due to persistent vomiting. The loss of chloride leads to low levels of potassium (hypokalaemia) as well. Hypokalaemia: Low potassium levels are commonly seen in cases of prolonged vomiting or conditions that lead to significant fluid loss. Epigastric mass: The presence of a palpable mass in the epigastric region is particularly indicative. In infants, this could suggest hypertrophy of the pyloric muscle, which is characteristic of pyloric stenosis. Differential Diagnosis Evaluation Now let’s evaluate each option: Bacterial gastroenteritis: Typically presents with diarrhea rather than isolated vomiting and would not usually cause an epigastric mass. Gastro-oesophageal reflux disease (GERD): While it can cause vomiting in infants, it does not typically present with an epigastric mass or significant electrolyte imbalances like hypochloraemic metabolic alkalosis. Obstructed umbilical hernia: This condition may cause vomiting but would more likely present with signs of bowel obstruction and pain rather than a specific epigastric mass. Pyloric stenosis: This condition is characterized by non-bilious projectile vomiting due to gastric outlet obstruction caused by hypertrophy of the pyloric sphincter muscle. The classic presentation includes electrolyte imbalances such as hypochloraemic metabolic alkalosis and hypokalaemia, along with a palpable “olive-like” mass in the right upper quadrant or epigastric area. Wilms’ tumour: Although it can present as an abdominal mass in children, it typically does not cause non-bilious vomiting or significant electrolyte disturbances like those described here. Conclusion Given all these considerations, the symptoms presented by this infant—non-bilious vomiting, hypochloraemic metabolic alkalosis, hypokalaemia, and an epigastric mass—are most consistent with: Pyloric stenosis

Answer 148

Explanation Mucosa For Ramstedt’s procedure to be effective, a longitudinal incision is made through the hypertrophied muscle as far as the mucosa; the mucosa is left intact and is seen bulging into the incision. If the mucosa is split during the procedure then it should be re-sutured. Circular muscle layer The incision is a sero -muscular incision as deep as the mucosa. An incomplete incision will result in continued gastric outflow obstruction. Longitudinal muscle layer The incision is a sero -muscular incision as deep as the mucosa. Serosa The incision is a sero -muscular incision as deep as the mucosa. Submucosa The incision is a sero -muscular incision as deep as the mucosa.

Answer 149

Explanation In cases such as this lifestyle modifying advice often has the desired effect In patients with mild symptoms, the first option should be lifestyle modifications like losing weight, giving up smoking, not eating within 2 h of lying flat and raising the head of the bed by 6–8 inches. It is usually treated by highly selective vagotomy in cases where trials of medication have failed If surgical intervention is needed then the treatment of choice is a Nissen’s fundoplication. Vagotomy has largely been superseded by proton pump inhibitors. It is usually worsened by smoking which acts to contract the lower oesophageal sphincter and increase oesophageal acidity Insufficient clearance of acid can contribute to the symptoms of gastro -oesophageal reflux disease (GORD), but this is not the most common problem which is incompetence of the lower oesophageal sphincter plus failure of the anatomical valve at the angle of His. It is worsened by smoking, the main action of which is to relax the lower oesophageal sphincter allowing stomach acid to enter the oesophagus. Other risk factors include obesity and alcohol, which also result in decreased competency of the lower oesophageal sphincter. Prokinetic drugs such as metoclopramide should be used as the treatment of choice in this condition If simple lifestyle modifications do not work then proton pump inhibitors and H 2 blockers should be tried before prokinetics. It leads to the development of Barrett’s metaplasia in 30% of cases Barrett’s oesophagus is seen in approximately 10% of patients undergoing endoscopy for investigation of GORD.

Answer 150

Explanation The best way of investigating gastro -oesophageal reflux disease is ambulatory pH monitoring in which a probe is placed within the oesophagus itself and provides a continu ous reading of the level of oesophageal acidity Twenty-four hour ambulatory monitoring was introduced in 1969 and has become the best way for monitoring the pattern of exposure of acid in the oesophagus, and the gold standard for gastro-oesophageal reflux disease. The monitor is placed so that the pH probe lies 5 cm above the oesophageal sphincter, therefore being able to record the presence of acid within the oesophagus itself. The oesophagus is a muscular tube approximately 25 cm long comprised of an inne r longitudinal muscle and an outer circular muscle coat which overlap in the middle part. The oesophagus is approximately 25 cm long, but comprises an inner circular muscle coat and an outer longitudinal coat, which is striated muscle in the upper part and smooth muscle in the lower part with considerable overlap in the middle. The lower oesophageal sphincter is a distinct anatomical condensation of muscle which together with the angle of His acts to present reflux of gastric acid back into the distal oesophagus. The lower oesophageal sphincter is a physiological rather than an anatomical sphincter and there is no distinct condensation of muscle here. Barrett’s oesophagus is diagnosed on the anatomical endoscopic appearance of the Z line. Barrett’s oesophagus needs to be diagnosed by endoscopy, with multiple biopsies to show metaplasia of the normal oesophageal squamous epithelium to columnar epithelium with goblet cells – it cannot be diagnosed from pH monitoring or the position of the Z line alone. There are three predictable sites of oesophageal constriction which relate to the cricopharyngeal sphincter (15 cm from incisors), where it is crossed by the aortic arch (22 cm) and where it passes through the diaphragm (38 cm) In addition to the three levels of constriction described there is a fourth which lies at 27 cm from the incisors and corresponds to the left principle bronchus.

Answer 151

Explanation Occurs more commonly in female patients Para-oesophageal hiatus herniae have an established preponderance of women affected. Can cause palpitations due to a relat ive increase in pressure on the underside of the thoracic diaphragm Palpitations can occur but this is though pressure on the vagus nerve. Symptoms usually relate to the mechanical effects of additional compression on the lower oesophagus, and patients commonly complain of dysphagia. Gastric volvulus is a recognised complication, but because of the elderly age group, surgery may be high risk. Are more common than sliding herniae Sliding hiatus herniae are the commonest type (95%). Occurs in a younger age group than sliding herniae Para-oesophageal hernias occur when a part of the stomach herniates through the oesophageal hiatus to lie next to the oesophago -gastric (OG) junction without herniation of the junction. The more common sliding hiatus hernia occur when the oesophagogastric junction herniates through the hiatus. Occurs when a part of the stomach herniates through the oesophageal hiatus with subsequent herniation of the gastro oesophageal junction Para-oesophageal hernias occur when a part of the stoma ch herniates through the oesophageal hiatus to lie next to the oesophago -gastric (OG) junction without herniation of the junction. The more common sliding hiatus hernia occur when the oesophagogastric junction herniates through the hiatus.

Answer 152

Explanation Sliding herniae are primarily associated with symptoms of GORD, whilst rolling herniae can cause gastric strangulation and necrosis and gangrene Complications include incarceration, gangrene and gastric volvulus. Oesophagitis is more commonly associated with sliding hiatus hernias. The majority of patients with hiatus herniae are symptomatic, and usually experience acid reflux The majority of hiatus herniae are sliding or axial in nature, are usually asymptomatic but can be associated with oesophagitis, stricture formation, dysphagia, chronic anaemia and inhal ational pneumonitis. Rolling herniae or para-oesophageal hiatal herniae usually affect elderly patients who present with intermittent dysphagia, pain after eating due to distension of the intrathoracic part of the stomach, cardiac symptoms such as palpitat ions due to pressure effects on the vagus nerve, and hiccups due to phrenic nerve irritation. As with gastro-oesophageal reflux disease, the most appropriate initial diagnostic modality is ambulatory pH monitoring Ambulatory pH monitoring is the gold standard for diagnosis of GORD, however, it is not usually necessary. The most appropriate investigation is more frequently upper GI endoscopy, upper GI contrast series or upper GI manometry to disprove other possible diagnoses (eg peptic ulcer disease), and to monitor chronic patients for signs of Barrett’s oesophagus. When GORD is associated with a proven sliding hiatus hernia, surgical management in the form of a Nissen fundoplication is the treatment of choice In severe cases of hiatus herniae, a Nissen fundoplication may be necessary but in the vast majority of patients symptoms can be managed by lifestyle modification and medications such as proton pump inhibitors and H 2 blockers. Despite the high fibre diet, paradoxically hiatus herniae are found more commonly in rural African communities The low fibre diet of westernised society, and also the prolonged sitting position for defecation, results in a higher incidence of hiatus herniae.

Answer 153

Explanation Following resuscitation an urgent OGD is a diagnostic option In a stable patient an urgent OGD is a relatively simple diagnostic test that can also be therapeutic if a bleeding source is identified. However, usually a computed tomography (C T) angiogram and selective embolization if the bleeding point can be identified would be indicated in this patient. The commonest cause of massive rectal bleeding is diverticulitis and this is usually painless Diverticular disease with erosion of small vessels in the bowel wall is the most common form of significant lower gastrointestinal haemorrhage and is usually painless. Diverticulitis however often presents with left iliac fossa (LIF) pain and pyrexia but is rarely associated with bleeding. The passage of bright red blood is never due to duodenal ulcer Fresh per rectal (PR) bleeding is usually from the lower GI tract, however, if bleeding is brisk, it may come from as high up as a peptic or duodenal ulcer, with the presence of blood promoting a fast transit time. It is usually controlled by catheter-directed infusion of vasopressin Vasopressin has little role in the management of this scenario – if they do not settle conservatively, then patients will need surgery. It may be localised by angiography if <0.5 ml/min Angiographic techniques can pick up bleeding at the rate of >0.5 ml/min in experienced hands.

Answer 154

Explanation Oesophageal achalasia which can be treated by dilating the lower oesophagus and associated sphincter Treatment of achalasia should initially be by lifestyle modification and medications to reduce lower oesophageal sphincter (LOS) pressure (eg nifedipine). Invasive treatments include balloon dilatation and also Heller’s cardiomyotomy together with a partial fundoplication to prevent excessive reflux. The most likely differential diagnosis in this man is oesophageal carcinoma In carcino ma, difficulties begin with swallowing solids and progress to include liquids. Normally this dysphagia is painless. In oesophageal carcinoma, dysphagia is progressive like achalasia While in carcinoma, difficulties begin with swallowing solids and progress to include liquids, in achalasia patients have equal difficulty in swallowing both liquids and solids. Achalasia which is characterised by incomplete lower oesophageal sphincter relaxation, decreased LOS tone and increased peristalsis of the oesophagus It is characterised by incomplete LOS relaxation, increased LOS tone and lack of oesophageal peristalsis. This results in dysphagia to both liquids and solids, chest pain that can be worse after eating, and unintentional weight loss. Although achalasia can be primary (affecting 1/100,000 individuals per year) it is much more commonly associated with other conditions Achalasia is a condition caused by failure of development of the lower oesophageal inhibitory neurons and involves the smooth muscle layers of the oesophagus and LOS. The most common form is primary achalasia but it also occurs associated with other conditions such as cancer or Chagas’ disease but much more infrequently.

Answer 155

Explanation If untreated may cause stricturing of the oesophagus If GORD goes untreated then a common eventual complication is oesophageal stricture. Does not require more than alteration of lifestyle to treat Often lifestyle alterations are successful, but should they not be medical management with proton pump inhibitor (PPI) or H 2 antagonists are frequently required. Further steps in management include gastric motility agents, then surgery. Is always present with hiatus hernia The majority of hiatus herniae are asymptomatic. Is preferably treated with surgery The initial management of mild cases is with lifestyle changes – these include weight loss, reducing smoking and alcohol intake, and avoiding food in the 2 h before be d. Should these fail or symptoms be more severe medical management with PPI or H 2 antagonists can be tried, followed by gastric motility agents. Surgery is only usually considered if symptoms remain following failure of lifestyle and medical management. Is treated surgically principally by attempting to narrow the gastro -oesophageal junction Surgical management is with a Nissen’s fundoplication in which the fundus is wrapped around the distal oesophagus with plication of the oesophageal hiatus. The gastro-oesophageal junction (GOJ) itself is not touched. This procedure can be performed open or laparoscopically.

Answer 156

Explanation Parastomal herniae are commonly asymptomatic Parastomal herniae are usually asymptomatic. Is more common when the stoma is brought through the rectus muscle Parastomal herniae occur in approximately 10% of colostomies and are usually asymptomatic. They rarely lead to complications and therefore usually do not need treating surgically. Factors that may increase the risk of developing a parasternal hernia include obesity, increasing age, post operative infection, malnutrition, and site of the stoma (stoma being placed outside of the rectus abdominus). Approximately 80 percent of patients with parastomal hernia remain asymptomatic and do not need further intervention. Occurs in 30% of colostomies Parastomal herniae occur in 10% of colostomies. Should always be repaired Since parastomal herniae are usually asymptomatic and rarely lead to complications treatment is not usually necessary. Should be repaired using a mesh Mesh repair can be undertaken, but the presence of foreign material around a stoma site leads to a high risk of infection, so this procedure is rarely carried out.

Answer 157

Explanation Appendicitis is associated with migratory right iliac fossa pain This feature of the history is part of the scoring process. Appendicitis is associated with a right shift in the neutrophil profile A left shift in the neutrophil profile is part of the scoring process, a right shift is not. Appendicitis is unlikely with a score over 5 If the score is less than 5 then appendicitis is unlikely, 5 –6 is equivocal, 7 or greater is likely. Does not count rebound tenderness in the marking scheme Rebound tenderness is an important part of the scoring process. Is associated with a higher mortality if the score is over 13 The score dose not predict mortalit y. Acute appendicitis has an associated mortality of 0.25% and a morbidity of 7.7%. It classically presents with periumbilical pain that then localises to the right iliac fossa, anorexia, nausea and vomiting. The patient will likely be tender in the right iliac fossa (RIF) and have signs of localised peritonism. The presentation is, however, variable because of the variability in position of the appendix and a high retrocaecal appendix may mimic cholecystitis, and appendicitis itself may be caused by a caecal carcinoma which occludes the appendix lumen. The peak incidence is towards 30 years of age with a second peak at 70 years. It has an overall incidence of 10% of the population. It is marginally more common in men (1.6 times). The Alvarado score is a clinical and laboratory based scoring system marked out of 10 which assesses the likelihood of the diagnosis of appendicitis:  if <5 appendicitis is unlikely  5–6 is equivocal and may require scanning  >7 is strongly predictive. Points are awarded as below: Migratory RIF pain (1 point), anorexia (1 point), nausea and vomiting (1point), RIF tenderness (2 points), rebound tenderness (1 point), fever (1 point), leucocytosis (2 points), left shift in neutrophils (1 point).

Answer 158

Explanation Men in the winter months It is more common in the winter months and in men. Children with this condition other have flu- like symptoms, and this effect, together with the predisposition to winter months, suggests virus involvement in the development of the condition. Women in the summer months Intussusception is less common in women and the summer months. Women in the winter months Intussusception is more common in men than in women, but is indeed more common in the winter months. Women regardless of the time of year Intussusception is more common in men than women. Men in the summer months While intussusception is more common in men, it is still more common in winter than in summer. Intussusception is the telescoping of one part of the intestine into the other and is most common in infants aged 4 months to 1 year, with peak incidence between 6 –9 months. Presenting features are abdominal pain, fever, ‘redcurrant jelly’ stool, and obstruction. Other risk factors include previous intussusception, or family history of the condition, and intestinal malrotation. An ultrasound scan (USS) or a barium or a ir enema may detect the point of intussusception. The enema may also relieve the intussusception, otherwise surgery may be required.

Answer 159

Explanation Ischiorectal abscess The ischiorectal (or ischioanal) fossae are prism-shaped fascia-lined potential spaces adjacent to the rectum. They are bordered by the levator ani muscle (superiorly and medially), the anal canal (medially), the perineal skin (inferiorly), and the ischial tuberosity (laterally). Ischiorectal abscesses are the second most common type of anorectal sepsis. Horseshoe abscess This option is an ischiorectal abscess that extends to both sides of the anal canal so forming a horseshoe shape. Intersphincteric abscess Intersphincteric abscesses sit between the internal and external sphincters. They may not be visible as they can be completely contained within the anal canal. In this instance either digital rectal examination or examination under anaesthetic (EUA) is required for diagnosis. Perianal abscess These are most common. They are superficial, do not transverse the external sphincter but sit just under the skin. Supralevator abscess These are the least common, they form from an upward extension of an intersphincteric abscess into the supralevator space. They may also form from an intra -abdominal inflammation (eg appendicitis) tracking down.

Answer 160

Explanation A laparoscopic cholecystectomy should be recommended Given the patient’s ongoing symptoms and thick-walled appearance to the gall-bladder, cholecystectomy should be considered. Differentials for a thic k-walled gall-bladder include the normal physiological state after food, cholecystitis (acute and chronic), infiltrative gall -bladder cancer, and liver conditions such as cirrhosis. Gallbladder carcinoma can be excluded This condition cannot be fully excluded without biopsy. She has acute cholecystitis Acute cholecystitis presents with right upper quadrant pain, fever and raised inflammatory markers. Murphy’s sign is usually positive (a positive Murphy’s sign is when pressure under the right costal margin o n inspiration results in pain and the patient ‘catching’ their breath). There can be fluid surrounding the gall-bladder as part of the inflammatory process. She has Mirizzi’s syndrome which is a gallstone that is eroding through the gallbladder wall into the ileum Mirizzi’s syndrome is obstructive jaundice caused by a large gallstone in Hartmann’s pouch compressing the common bile duct. Mirizzi’s syndrome is one of the indications to convert from laparoscopic cholecystectomy to an open procedure, often leav ing Hartmann’s pouch behind to fibrose. The common bile duct is dilated Six millimetres is the upper limit of normal for common bile duct diameter, and allowances of a few millimetres more may be made in elderly patients.

Answer 161

Explanation Patients with both ulcerative colitis and primary sclerosing cholang itis are at higher risk of requiring proctocolectomy than patients with ulcerative colitis alone Indications for proctocolectomy in ulcerative colitis (UC) include (non-exhaustive list):  Acute/emergency – toxic mega-colon, fulminant UC uncontrolled by medical treatment, perforation, uncontrolled bleeding.  Elective – chronic steroid dependency or systemic side-effects from treatment, dysplasia or adenocarcinoma on biopsy, refractory disease despite medical management.  PSC, in particular, is associated with an increased risk of developing colorectal cancer so, in line with the above indications, is more likely to require restorative proctocolectomy. Pouch surveillance is mandatory in all cases of ulcerative colitis Pouch surveillance is recommended for tho se who have colonic dysplasia or neoplasm, as there are rare case reports of neoplasm developing within the pouch. It is not mandatory in all cases of UC. Pouchitis is common with restorative procotocolectomy After 10 years around 50% of patients will have had their first episode of pouchitis. The incidence of pouch failure is 5–15% per year and reasons include pelvic sepsis, poor function and pouchitis. Restorative proctolcolectomy is a three-stage procedure Reoperative pelvic surgery (RPC) should be a one stage or two stage operation (if a defunctioning stoma is employed). Further descriptive evidence may be found via the links below. Restorative proctocolectomy is contra-indicated in patients who have an internal anal sphincter defect Contraindications fo r restorative proctocolectomy pouch formation include small bowel disease involvement (eg in Crohns) and anal disease involvement (eg in Crohns, or low rectal cancers). Ulcerative colitis starts as a proctitis and ascends in a continuous fashion affecting up to the entire colon, but typically not the small bowel. However, incompetent ileocaecal valves are not uncommon and can lead to a ‘backwash’ ileitis, making distinction from Crohn’s or a mixed colitis difficult. UC has many extra-intestinal manifestations, such as uveitis, arthritis, primary sclerosing cholangitis and erythema nodosum. It is associated to the HLA-B27 phenotype. Restorative proctocolectomy is a procedure by which a pouch from terminal ileum is fashioned and anastomosed to the anus, 1–2 cm above the dentate line. The pouch is usually J in shape and measures 15 cm in length. RPC is most commonly recommended in ulcerative colitis and familial adenomatous polyposis where the colon needs to be removed to eliminate the risk of colon cancer. Ideal pouch function is approximately 4–6 times per day and two times at night. The benefit of the pouch is to eliminate urgency from a simple ileo -anal anastomosis, and avoid a permanent ileostomy.

Answer 162

Explanation Open repair requires fixation of mesh to the reflected edge of the Inguinal ligament An inguinal hernia emerges above and medial to the pubic tubercle, so in this patient we suspect an inguinal hernia. The inguinal canal in women contains the round ligament of the uterus and a remnant of the processus vaginalis. A persistent processus vaginalis in women forms the canal of Nuck. The floor of the inguinal canal is formed by the reflected edge of the inguinal ligament. As part of the Lichtenstein procedure the lower part of the mesh is fixed to this reflected edge of the inguinal ligament with the mesh above this positioned to reinforce the posterior wall of the canal. In women a direct hernia is more likely than an indirect one Direct hernias are rare in women (man to woman ratio 10:1), they result from an acquired weakness of the wall of the inguinal canal formed by the transversalis fascia. Indirect hernias occur through the internal inguinal ring where there is an inherent weakness. Direct hernias occur usually in the elderly population, whereas indirect hernias can occur at any age and can be congenital. Repair requires preservation of the round ligament During repair the round ligament can be divided. The diagnosis is that of an femoral hernia which is more common than an inguinal hernia in women Femoral hernia accounts for 20% of hernias in women and 5% of hernias in men. The man to woman ratio of inguinal hernia is 10 to 1. The hernia can be repaired with a local anaesthetic block to L2 and L3 Inguinal hernia can be repaired by a local anaesthetic block that requires infiltration of the iliohypogastric and ilioinguinal nerves (T12 and L1), 2 cm medial from the ant erior superior iliac spine, the genitofemoral nerve (L1 and L2), 1–2 cm lateral to the pubic tubercle and local infiltration of the subcutaneous tissues along the line of incision.

Answer 163

Explanation Colonoscopy The differential here is rectal neoplasm, polyp and varices. The best investigation would be an endoluminal one, ie colonoscopy. Biopsies should only be considered if the mass is not of a vascular nature as attempting to biopsy a varices would likely lead to heavy bleeding. In patients that are unfit for colonoscopy axial imaging may be considered. Computerized tomography scan of the abdomen and pelvis This is not the best initial diagnostic investigation. Capsule endoscopy Capsule endoscopy is a useful investigation to image the small intestines, however for a low colonic mass a different endoluminal investigation would be far more useful. Low anterior resection This may be the treatment of choice, for example if a malignancy is diagnosed. It is not, however, a diagnostic investigation. Magnetic resonance imaging (MRI) of the pelvis This is part of the imaging required for the local staging of rectal cancers, it is not the best initial diagnostic investigation. Along with the differentials of rectal neoplasm or polyp, this patient’s history of cirrhosis means that varices must also be considered on the differential list. Common sites for varices are as follows:  In the gastro-oesophageal region, the oesophageal tributaries of the left gastric vein anastomose with the oesophageal veins, which empty into the azygos vein.  In the paraumbilical region the paraumbilical veins in the falciform ligament anastomose with the subcutaneous veins in the anterior abdominal wall.  In the anorectal region the superior rectal vein anastomoses with the middle and inferior rectal veins, which are anastomoses of the internal iliac and internal pudendal veins.

Answer 164

Explanation Circular muscle The circular muscle is the last layer to be divided. Longitudinal muscle The longitudinal muscle sits outside the circular muscle. Mucosa The mucosa is left intact. Parietal peritnoneum The peritoneum is divided to gain access to the greater curvature of the stomach. Serosal surface The serosa is cut through before the muscular layers being divided. Ramstedt’s pyloromyotomy is indicated in hypertrophic pyloric stenosis. An incision is made along the length of the hypertrophic muscle, and the layers of longitudinal and circular muscle are divided until the mucosa is exposed.

Answer 165

Explanation 2% Diltiazem ointment The accepted treatment protocol for anal fissures is firstly topical 0.2% glyceryl trinitrate(GTN) or 2% Diltiazem followed by Botox and then lateral sphincterotomy or advancement flap. The latter is considered in women with low pressure anal fissure. Anterior anal fissures are commoner in women due to the lack of support to the anal canal anteriorly, bu t posterior fissures are most common overall. Advancement flap An advancement flap is considered in low pressure anal fissure, but is not first -line treatment. Examination under anaesthesia and Botulinum A toxin Examination under anaesthesia is not usually indicated for primary anal fissure – it may, however, be necessary in elderly patients or other groups in whom a secondary cause is suspected. Additionally, in the paediatric group if abuse is considered, a possible cause examination under anaesthesia (EUA) may be indicated. Botulinum toxin is a useful treatment causing relaxation of the sphincter, improving blood flow and therefore healing time, but is usually considered after other topical treatments have failed. Flexible sigmoidoscopy and high fibre diet Whilst a high fibre diet is important in both prevention and treatment of primary anal fissure it is not thought to offer much benefit in the treatment of chronic anal fissures. Additionally a flexible sigmoidoscopy is not usually a first -line measure in young patients when primary anal fissure is suspected. However, in elderly patients, secondary causes such as anal or rectal cancer are more likely and further investigation may be indicated. Lateral sphincterotomy Lateral sphincterotomy can be considered should topical treatments or Botox management not prove successful. The aim is to reduce the pressure of the sphincter, which aids blood flow to the area and therefore healing.

Answer 166

Explanation Alcohol The most common cause of chronic pancreatitis is chronic excess alcohol. Cholelithiasis Cholelithiasis (gallstones) and choledocholithiasis (gallstones in the common bile duct) are common causes of acute pancreatitis, which with alcohol accounts for approximately 80% of cases. Hypocalcaemia Hypocalcaemia is a complication of acute pancreatitis, as opposed to hypercalcaemia which is a cause. Hypothermia Hypothermia is a recognised cause of acute pancreatitis but alcohol is the most likely cause in this scenario. Mumps Viral infections such as mumps are also well recognised causes of acute pancreatitis, but alcohol is the most likely cause in this scenario.

Answer 167

Explanation Securing IV access The clinical vignette suggests a patient with decompensated liver disease (ascites, confusion) as a result of heavy drinking. The suspicion must therefore be that this patient has presented with a variceal haemorrhage. Oesophageal varices may present with profuse haematemesis and this patient should be initially approached with an AB CDE assessment. As part of this, IV access should be secured and bloods sent including an urgent crossmatch. Administration of vasoactive drugs such as somatostatin or octreotide If urgent endoscopy is available then this should occur as soon as possible in a patient with active variceal bleeding. If not, then vasoactive drugs such as somatostatin, octreotide or Glypressin should be considered. These would require an IV line to be placed to be administered. Balloon tamponade using a Sengstaken–Blakemore tube Balloon tamponade is considered normally only if band ligation or sclerotherapy fails to adequately control the patient’s variceal haemorrhage, or in an emergency setting when endoscopy is not available. Performing TIPS procedure as an emergency Transjugular intrahepatic portosystemic shunt (TIPS) procedure can be used to reduce portal pressure by diverting portal blood flow into the hepatic vein and may be used if other methods firstly cannot control bleeding. Performing an urgent oesophago -gastroduodenoscopy (OGD) and endoscopic band ligation In patients with variceal bleeding this procedure is the most important immediate definitive management, however it does not supersede a basic ABCDE (Airway maintenance with cervical spine protection, Breathing and ventilation, Circulation with haemorrhage control, Disability: neurological status, Exposure/environmental control) assessment and resuscitation of the patient.

Answer 168

Explanation Incontinence The commonest of the correct options listed here is faecal incontinence (75%), which may actually be the patient’s presenting symptom. Alternatively constipation can very commonly be either the presenting symptom or a complication. Rectal prolapse is a condition that most commonly affects older women, but can occur in any age. Partial rectal prolapse (prolapse of the mucosal layer only) occurs more commonly in children while complete rectal prolapse (prolapse of all layers of the rectum) is typical in elderly women. Patients may present because they have felt/noticed the prolapse, often while straining to pass stool. Additionally they may present with symptoms such as incontinence, constipation, per rectal (PR) ble eding or pain. Diagnosis may be simple with the prolapse visualised either at rest or on straining/performing the Valsalva manoeuvre. Imaging may be required in some patients, for example an evacuating proctogram. Incarceration Incarceration is a complicat ion of rectal prolapse, however, it is not the commonest of the correct options listed here. Rectal carcinoma Occasionally a prolapse can be a presenting feature of rectal carcinoma. Strangulation This is a complication of rectal prolapse that requires emergency surgery. It presents with a painful non-reducible prolapse. It is not the most common of the options listed. Ulceration Ulceration and necrosis of the rectal wall are common complications, albeit not the most common listed option.

Answer 169

Explanation The majority resolves with conservative treatment Most cases of partial rectal prolapse in children resolve with conservative treatment. It involves all layers of the rectal wall Complete rectal prolapse involves all layers of the rectal wall and is more commonly seen in elderly women. Partial rectal prolapse is more common in children and involves the mucosal layer only. It is associated with a significant increased risk of r ectal carcinoma There is an associated risk of rectal carcinoma in adults with complete rectal prolapse, but this risk has not been reported in children with partial rectal prolapse; it may be more commonly associated with cystic fibrosis, Ehlers–Danlos or Hirschsprung’s disease. It is more common in adults than children In adults complete rectal prolapse is more common, in children partial rectal prolapse is more common. It should be treated with Delorme’s procedure Delorme’s procedure is excision of the mucosal component of a prolapse with plication of the muscle from below, and is generally used in adults.

Answer 170

Explanation Tuberculosis The patient’s country of origin, Uganda, where tuberculosis (TB) is endemic, along with the history of chronic cough and weight loss are highly suspicious for tuberculosis infection. Low and high fistula are defined by the level at which they pass through the anal sphincters. A low fistula’s internal orifice is below puborectalis. A high fistula’s orifice begins above this. The former are common, relatively easy to manage and do not usually threaten the patient’s sphincteric muscle function (and therefore continence). High fistulae are infrequent, complex to manage and can lead to incontinence. Carcinoma This option is a possibility, and should certainly be considered given the weight loss red flag. It is unlikely in a patient of this age, and does not explain h is cough and therefore is not the most likely option. Crohn’s disease All the options listed are possible causes of high fistula. Crohn’s disease is a recognised cause in this age group and the weight loss would fit with this diagnosis. Crohn’s disease is, however, more common in smokers and this option does not explain the chronic cough. Diverticular disease All the options listed are possible causes of high fistula. Diverticular disease is possible, but uncommon in younger patients. Ulcerative colitis Ulcerative colitis is a recognised cause in this age group and the weight loss would fit with this diagnosis, however, this option also does not explain the chronic cough from which the patient has been suffering.

Answer 171

Explanation Institutionalised and immobile elderly patients are at increased risk This is correct, other risk factors include cerebral palsy, Parkinson’s disease or other neurological disorders; chronic renal, pulmonary or cardiac disease; prolonged immobility; and prolonged use of narcotic drugs and other anticholinergic drugs that reduce bowel motility. Chronic colonic pseudo-obstruction is characterised by symptoms of recurrent bowel obstruction, abdominal bloating and/or pain, evidence of bowel obstruction on radiographic imaging, and no evidence of anatomic/structural abnormality. Possible complica tions include diarrhoea (and associated electrolyte disturbances), intestinal perforation, nutritional deficiencies and weight loss. A barium enema is likely to demonstrate a mechanical cause Pseudo-obstruction is not caused by a mechanical obstruction, instead it is a result of ineffective peristalsis of the intestine. The condition is not commonly associated with physical trauma Physical trauma is a common cause of pseudo -obstruction. The condition is rarely associated with electrolyte disturbances Weight loss and electrolyte disturbances are common occurring as a result of loss of appetite, frequent vomiting and poor nutritional intake. Additionally, the causative conditions in secondary pseudo-obstruction (eg Parkinson’s disease, cerebral palsy, immobility, or chronic renal failure) may impair the patient’s ability to take on adequate/appropriate nutrition or may directly lead to electrolyte disturbances themselves. The condition may successfully be treated by gastroscopy Colonoscopy is often successful in decompressing the colon, although symptomatic relief from this is often temporary.

Answer 172

Explanation Increased synthesis of VLDL (very-low-density lipoprotein) Hypertriglyceridaemia occurs frequently in association with a high alcohol intak e, and is due to the increased synthesis of triglyceride for incorporation into VLDL in the liver. This is thought to be as a result of the altered redox state as a consequence of alcohol metabolism, which favours fat synthesis Decreased pancreatic lipase secretion Pancreatic lipase is normally secreted into the gut and higher plasma levels are found in pancreatitis Deficiency of apolipoprotein C-II Apolipoprotein C-II activates lipoprotein lipase, which is responsible for the clearance of very- low-density lipoprotein (VLDL) and chylomicrons from the plasma. Both lipase deficiency and apolipoprotein C-II deficiency are rare, inherited causes of severe hypertriglyceridaemia, which usually present in childhood. Deficiency of LDL (low-density lipoprotein) recep tors LDL receptors are involved in the transport of cholesterol from the plasma to the interior of cells: deficiency is the cause of familial hypercholesterolaemia. Deficiency of lipoprotein lipase Lipoprotein lipase deficiency is a rare inherited cause of severe hypertriglyceridaemia. The condition usually presents in childhood. Lipoprotein lipase is responsible for the clearance of very-low-density lipoprotein (VLDL) and chylomicrons from the plasma.

Answer 173

Explanation Cystic fibrosis Most newborn babies with meconium ileus have cystic fibrosis. Cystic fibrosis (CF) is an autosomal-recessive disorder associated with the production of abnormal mucous with high salt content. The Guthrie tests done in the first days of life include a spot test for CF, however, a sweat chloride test is used to confirm the diagnosis. Meconium ileus occurs in CF as a result of the following: the pancreas undergoes dysplasia, so with the loss of pancreatic enzymes and presence of abnormal mucous, thick meconium forms. This is thick enough to causes intraluminal intestinal obstruction usually at the level of the terminal ileum. Affected bowel will be dilated and filled with heavy meconium making it prone to volvulus. Hirschsprung’s disease Hirschsprung’s disease results from abnormal development of the intrinsic nerves of the colon and results in megacolon, rather than meconium ileus. Intussusceptions Intussusception is a common paediatric cause of obstruction, classically presenting with passing of a ‘red currant jelly’ stool and signs of obstruction. It results from part of the bowel ‘folding’ into an adjacent section of bowel such that it becomes trapped within the lumen of the adjacent section. Duodenal atresia This condition is the congenital a bsence of the duodenal lumen. It may be detected antenatally as it is a cause of polyhydramnios, in newborns it will present with features of intestinal obstruction. Imperforate anus This is a congenital absence or obstruction of the anal passage, which wi ll be quickly detected as part of the routine newborn screening examination.

Answer 174

Leiomyoma Leiomyoma is the commonest benign tumour that occurs commonly in the lower part of the oesophagus, although it is still a relatively rare growth. Overall benign tumours of the oesophagus make up approximately 1% of all oesophageal tumours, and leiomyomas are around two-thirds of this, or 0.6% of all oesophageal tumours. The majority of these are asymptomatic. The commonest symptomatic presentation is dysphagia. The tumours are well encapsulated. Endoscopic resection for small pedunculated lesions and localised resection for larger lesions is the treatment if symptomatic. Fibroma Fibromas do occur, but are very rare and certainly not as common as leiomyomas. Pseudopolyps Pseudopolyps can occur, these are typically inflammatory in nature as a result of repetitive inflammation/ulceration followed by deposition of granular tissue/regrowth of norma l tissue. Adenoma Adenomas do occur, but are very rare and certainly not as common as leiomyomas. Fibrous polyps The second commonest benign tumours are fibrous or fibrovascular polyps that occur commonly in the upper third of the oesophagus. Most of the tumours of the oesophagus are malignant and symptomatic benign tumours account for less than 1% of oesophageal tumours.

Answer 175

Explanation Usually limited to mucosa Crohn’s is typically a transmural inflammatory process There are abnormal areas intervening between normal mucosa ‘skip lesions’ In Crohn’s disease there are often abnormal areas intervening between normal mucosa, these are called ‘skip lesions’. Ulceration in the bowel is usually deep The inflammation is transmural and ulceration are typically deep. This situation leads to a predisposition to fistulae formation, perforations, abs cesses and strictures. Non-caseating granuloma Granuloma are a histological feature of Crohn’s disease. May affect any part of the alimentary tract In ulcerative colitis the rectum is always affected, however in Crohn’s disease any part of the alimentary tract may be affected. Perianal disease is common in Crohn’s disease presenting with features such as fissures, abscesses and fistulae. Mouth ulcers can also be a presenting feature. Crohn’s disease is an inflammatory bowel disease that affects any part of the alimentary tract. Patients are typically diagnosed before the age of 30, and it affects any ethnic group, but mostly white patients and Ashkenazi Jews. Family history of the disease is a risk factor, and current cigarette smoking is a very strong risk factor and also associated with more severe disease and an increased likelihood of needing surgery. Presenting symptoms of gastrointestinal disease (ie not extra-intestinal manifestations) frequently include weight loss, loss of appetite, abdominal pain, diarrhoea with blood in stool. Additionally, mouth ulcers and perianal disease are common in Crohn’s presenting with features such as fissures, abscesses and fistulae. The inflammation is transmural affecting the whole thickness of the affected bowel and no n-caveating granulomas are typically found. The terminal ileum is affected in nearly 75% of the cases. As the inflammation is transmural and the ulcers associated with the disease are deep, fistulae formation, perforations, abscesses and strictures are not unusual. Inflammatory bowel diseases are associated with extra - intestinal manifestations that affect the skin (pyoderma gangrenosum, erythema nodosum), eyes (iritis), joints (sacroiliitis, ankylosing spondylitis), biliary tree (sclerosing cholangitis, chr onic active hepatitis).

Answer 176

Explanation Bile salt deposition in the skin can cause intense itching Biliary obstruction leads to accumulation of bile salts with backflow into the liver and systemic circulation, raising their blood concentration and leading to skin deposition and pruritus. Clinically detectable jaundice does not occur until the bilirubin is above 60 µmol Clinically detectable jaundice occurs above 30 µmol/l, at 60 µmol/l the jaundice should be obvious. Most biliary strictures are due to inflammatory scarring after chole cystitis Most biliary strictures are iatrogenic after surgery, only small numbers are post inflammatory disease. Cholangiocarcinoma is the commonest neoplasm causing obstructive jaundice Adenocarcinoma of the head of the pancreas is the commonest neoplasm leading to obstructive jaundice. Ninety per cent of pancreatic carcinomas are adenocarcinomas derived from the ductal cells of the exocrine pancreas; these have only a 5% 5 -year survival rate. Cholangiocarcinoma is a rare tumour arising from biliary epithe lium. Unlike adenocarcinoma of the pancreas these tumours are slow growing and often metastasise late so that complete resection is often possible – nevertheless they have a poor prognosis. Primary sclerosing cholangitis (PSC) is more commonly seen in Croh n’s disease than in Ulcerative colitis Primary sclerosing cholangitis is a rare condition thought to be of autoimmune origin; it results in progressive fibrosis of the biliary system. PSC may arise spontaneously but is usually in association with long-standing UC, rather than Crohn’s disease. Areas of short localised disease can be treated with an indwelling stent.

Answer 177

Explanation Normal architecture Hepatitis A virus has no known chronic carrier state and does not lead to chronic hepatitis or cirrhosis. If a liver biopsy is performed after the patient has completely recovered from this infection it will therefore show normal architecture. Central necrosis Central necrosis is a finding of acute hepatitis. Chronic septal fibrosis This option a part of the histological findings of chronic hepatitis. Lobular fibrosis This option is a part of the histological findings of chronic hepatitis. Periportal fibrosis This option is a part of the histological findings of chronic hepatitis. It is also found in schistosomiasis. Hepatitis A virus is a single-stranded RNA picornavirus. This virus is the most common cause of acute viral hepatitis and is particularly commo n in children and young adults. In some countries more than 75% of adults have been exposed. Hepatitis A virus spreads primarily by faecal–oral contact and so can occur in areas of poor hygiene. Water -borne and food-borne epidemics occur, especially in underdeveloped countries. Eating contaminated raw shellfish is sometimes responsible. Sporadic cases are also common, usually as a result of person-to-person contact. Faecal shedding of the virus occurs before symptoms develop and usually ceases a few days after symptoms begin. This means that infectivity often has already ceased when the hepatitis becomes clinically evident. Hepatitis A virus has no known chronic carrier state and does not lead to chronic hepatitis or cirrhosis. If a liver biopsy is performed after the patient has completely recovered from this infection it will therefore show normal architecture.

Answer 178

Explanation Haemolysis Haemolysis results in the destruction of red cells therefore anaemia. Destruction of red cells also leads to the increased production of unconjugated bilirubin. Fibrosis of the common bile duct This option would cause an obstructive pattern of jaundice, the patient’s direct (conjugated) bilirubin would be expected to be significantly more elevated than here. Hepatitis Hepatitis typically causes a non-obstructive pattern of jaundice, as this patient’s blood tests suggest. However, it does not explain the anaemia. Sclerosing cholangitis This option would cause an obstructive pattern of jaundice, the patient’s direct (conjugated) bilirubin would be expected to be significantly more elevated than here. Schistosomiasis Schistosomiasis typically causes a non-obstructive pattern of jaundice, as this patient’s blood tests suggest. However, it does not explain the anaemia. Hyperbilirubinaemia results from increased bilirubin production, decreased liver uptake or conjugation, or decreased biliary excretion. Total bilirubin normally is mostly unconjugated, with values of <1.2 mg/dl ( <20 μmol/l). Fractionation can measure the proportion of bilirubin that is conjugated (or direct, ie measured directly). Fractionation is r equired only in neonatal jaundice or if the bilirubin is elevated, but the other liver test results are normal, suggesting that hepatobiliary disease is not the cause. Unconjugated hyperbilirubinaemia (indirect bilirubin fraction > 85%) reflects increased bilirubin production (for example when haemolysis is the case, as in this scenario) or defective liver uptake or conjugation (eg in hepatitis, or Gilbert’s syndrome). Such increases in unconjugated bilirubin are generally less than five -fold ( <6 mg/dl or <100 μmol/l) unless there is concurrent liver disease. Conjugated hyperbilirubinaemia typically suggests decreased biliary excretion, also known as obstructive jaundice. Common causes of this condition include gall stones, cancers (such as head of pancreas tumours), chronic inflammatory diseases such as primary sclerosis cholangitis, and iatrogenically following procedures such as ERCP.

Answer 179

Explanation Pseudopolyps Pseudopolyps are a classic finding of ulcerative colitis. This diagnosis is suggested by presence of sclerosing cholangitis (an extra-intestinal manifestation) along with the bloody diarrhoea in the scenario above. Colonic adenocarcinoma This answer is not correct, it does not explain the sclerosis cholangitis. Diverticulitis Diverticulitis is not usually a chronic complaint, it is an acute inflammation of diverticula typically in the distal colon. It presents typically with left iliac fossa tenderness, bloody diarrhoea, and fever. Granulomatous inflammation Granulomatous inflammation suggests Crohn’s disease, however, Crohn’s is not classically associated with sclerosing cholangitis. Villous adenoma A villous adenoma is a non-malignant polyp that is most commonly found within the colon. They can result in diarrhoea, typically not bloody diarrhoea though. They have considerable potential to develop into malignant adenocarcinoma. Ulcerative colitis affects the mucosa and submucosa of the rectum and colon, with a sharp border between normal and affected tissue. Only in severe disease is the muscularis layer involved. In early cases, the mucous membrane is erythaematous, finely granular and friable, with loss of the normal vascular pattern and often with scattered haemorrhagic areas. Large mucosal ulcers with copious purulent exudate are characteristic of severe disease. Islands of relatively normal or hyperplastic inflammatory mucosa project above areas of ulcerated mucosa – these are name pseudopolyps. Fistulas and abscesses do not occur, unlike in Crohn’s disease.

Answer 180

Explanation Sclerosing cholangitis Primary sclerosing cholangitis is a chronic cholestatic syndrome characterised by patchy inflammation, fibrosis and strictures of the intrahepatic and extrahepatic bile ducts. These patchy affects are what led to the classic ‘beaded’ appearance mentioned in the scenario above. Around 80% of patients with PSC have inflammatory bowel disease, often ulcerative colitis. Symptoms of fatigue and pruritus develop late. The diagnosis is based on contrast cholangiography (with endoscopic retrograde cholangiopancreatography) or magnetic resonance cholangiopancreatography. The disease leads to eventual obliteration of the bile ducts, with cirrhosis, hepatic failure and sometimes cholangiocarcinoma. Acute cholecystitis Cholecystitis presents with Murphy’s positive right upper quadrant pain and signs of infection. On imaging the gall-bladder may appear thick-walled and with some surrounding fluid. Chronic cholelithiasis Chronic cholelithiasis may well be asymptomatic, or may present with symptoms of biliary colic. Imaging will reveal gallstones within the gall-bladder. Cholesterosis Otherwise known as ‘strawberry gall-bladder’, this condition gives the wall of the gall-bladder a strawberry-like colour and visual texture as a result of hig h cholesterol. Gallstone ileus Gallstone ileus is mechanical obstruction of the bowel due to a gallstone.

Answer 181

Explanation Duodenal ulcer Duodenal ulcers tend to be associated with a fairly consistent pattern of pain. Pain is absent when the patient awakens but appears mid-morning, is relieved by food, but recurs 2–3 h after a meal. Pain that awakens a patient at night is common and is highly suggestive of duodenal ulcer. Duodenal ulcers are more common than gastric ulcers. Gastritis Gastritis pain is usually intermittent and described as indigestion or ‘burning’ pain, it is typically worsened shortly after eating food. Gastric ulcer Gastric ulcer pain also tends to be relieved by food, and come back a few hours later. Pain at night being common. They are not, however, as common as duodenal ulcers. Pyloric stenosis Pyloric stenosis is extremely rare in adults. It presents with vomiting after meals and weight loss as patients are not usually able to adequately nourish themselves. Zollinger-Ellison syndrome This is a rare condition. Gastrinomas within either the pancreas or duodenum secret the hormone gastrin, this hormone results in increased acid production within the stomach uncontrolled by normal feedback loops. Excessive acid production then results in large numbers of gastric and duodenal ulcers.

Answer 182

Explanation Is caused by chronic reflux of gastric acid into the lower oesophagus causing metaplasia of the normal squamous epithelium of the lower oesophagus to columnar and goblet cell epithelium. The chronic reflux of gastric acid into the lower oesophagus causes chronic inflammation. As a result of this inflammation there is metaplasia of the affected oesophageal epithelium from squamous epithelium to columnar epithelium with goblet cells. Later dysplasia can occur and eventually this can develop into malignancy. Occurs in approximately 40% of patients with gastro-oesophageal reflux disease (GORD) in the long term Around 5–15% of patients with gastro -oesophageal reflux disease (GORD) will develop Barrett’s oesophagus (metaplasia), which in turn is associated with an increased risk of oesophageal malignancy (neoplasia). Presents with malignancy in one-third of cases The risk of developing oesophageal cancer in people with Barrett’s is 0.13 %. About 1 in 860 patients with Barrett’s go on to develop cancer (Cancer Research UK). Is diagnosed by the position of the z line which rises from its normal position The histological changes (from squamous to columnar epithelium with goblet cells) together with elevation of the Z line on oesophago -gastro-duodenoscopy (OGD) is diagnostic. The Z line usually lies 3 cm from the lower oesophageal sphincter and is identified by a change in colour from salmon pink to a deeper red. Histamine H2 blockers are the treatment of choice The treatment of choice is with proton pump inhibitors and close follow up.

Answer 183

Explanation It may present with large bowel obstruction Obstruction is unusual but well recognised. Often this is a result of fibrous tissue development and stricturing following an episode, or several episodes, of diverticulitis. Diverticular perforation is a common and important complication of diverticular disease and can be managed medically or surgically depending on the Hinchey Classification. Fistulae to bladder, skin, vagina and other loops of bowel are also common complications. It is frequently associated with electrolyte d isturbances Diverticulae are very common and often asymptomatic. Presenting features can include persistent pain, irregular bowel habit including diarrhoea or constipation (or alternating). Complications are also common presenting features, most commonly diverticulitis. It is a premalignant disease Colonic diverticular disease is not related to colon cancer but shares common dietary factors with colorectal carcinoma. It is usually an inherited condition Colonic diverticular disease is not inherited. The biggest risk factor is lack of dietary fibre and it usually occurs in older patients. It may cause a vesicovaginal fistula Fistula to bladder, skin, vagina and other loops of bowel are common but not vesicovaginal fistulae.

Answer 184

Explanation TNM stage I disease While most gall-bladder carcinoma presents at a late stage and has a poor survival, if detected early prognosis is much better. At stage 1A (T1, N0, M0) – simple cholecystectomy, should be curative. At stage IB (T2, N0, M0) extended cholecystectomy is performed conveying a 5 -year survival rate of 70–90%. The tumour is usually an adenocarcinoma, although in 10% of patients squamous cell carcinoma may occur. Adenocar cinoma, particularly papillary adenocarcinoma, is associated with the best prognosis. Age Age is a recognised risk factor for carcinoma of the gall-bladder, with the incidence rising with age. It is most commonly diagnosed in those greater than 65 years of age. Female Female gender is a recognised risk factor for carcinoma of the gall-bladder, with a 2:1 female to male ratio. This may be due to the increased frequency of cholelithiasis in women. Presence of gallstones Over 75% of patients with gall-bladder cancer have cholelithiasis. Other important predisposing conditions include chronic cholecystitis, porcelain gall-bladder, gall-bladder polyps and choledochal cysts. TNM of T4, any N, M0 Gall-bladder carcinoma usually presents at a late stage and stage III disease (T4, any N, M0) is generally not surgically curable (a 1-year survival rate for advanced gall-bladder cancer is less than 5% with a median survival of 2–4 months).

Answer 185

Explanation It is associated with alcoholic liver disease Alcoholic liver disease is strongly associated with hepatocellular carcinoma. I t is considered a causative factor in up to 45% of hepatocellular carcinoma cases (in American and Italian studies. Alcohol is causative through two possible mechanisms – direct genotoxicity and because excessive chronic alcohol consumption leads to cirrho sis. Women are affected more than men Men are more commonly affected than women. Worldwide this ratio varies between 2:1 and 4:1. In hepatitis B virus endemic areas it usually presents above the age of 50 In the UK the average age of presentation is 66, in countries with endemic hepatitis B there are peaks in the age distribution at 45 and 65. It is associated with HIV Common viral risk factors include hepatitis B and C viruses (HBV and HCV). In Europe and North America anti-HCV antibodies are present in around 70% of patients with hepatocellular carcinoma (HCC). In countries with endemic hepatitis B, 90% of patients with HCC are positive for hepatitis B. HIV is not an independent risk factor for HCC although co -infection with HCV and HIV may lead to more rapid progression to HCC. Serum a-fetoprotein levels (AFP) are normal AFP levels are usually raised. Patients with cirrhosis due to HBV, HCV, alcohol, primary biliary cirrhosis or haemochromatosis should be offered a 6 -monthly abdominal ultrasound scan and serum AFP test as screening for hepatocellular carcinoma. Clinical features of hepatocellular carcinoma include weight loss, anorexia, fever, a right upper quadrant pain and ascites. Chemotherapy and radiotherapy are generally unhelpful. Survival, except in very selected groups, is seldom more than 6 months.

Answer 186

Explanation It is associated with human papillomavirus infection The human papillomavirus (usually type 16) may cause intraepithelial neoplasia, which with time progresses to anal carcinoma. This virus is found in approximately 70% of patients. Other risk factors for anal carcinoma include a history of cervical or vaginal cancer, history of sexually transmitted disease and immunosuppression following solid organ transplantation. It characteristically presents with faecal incontinence Rectal bleeding is the most common initial symptom (45% of cases); 30% of patients complain of pain or a sensation of a mass. It does not metastasise Anal cancer can metastasize. The nodal metastatic locations depend on the lymphat ic drainage, which is dependent on where the anal cancer originates: above the dentate line, flows to the perirectal and paravertebral nodes; below the dentate line, drainage is through the inguinal and femoral nodes. The most common site of distal metasta sis is the liver. It is relatively radioresistant Anal carcinoma is relatively radiosensitive. Presently, combination radiotherapy and chemotherapy [fluorouracil (5-FU) ± mitomycin or 5-FU + cisplatin] is used as initial standard first-line treatment. Abdo minoperineal (AP) resection is reserved for recurrent or resistant tumours. It is related to increased dietary fat intake Increased dietary fat intake is thought to be a risk factor for colorectal cancer, not for anal cancer.

Answer 187

Explanation Incidence is higher in patients with pernicious anaemia Risk factors for developing gastric cancer include the presence of H. pylori, blood group A, pernicious anaemia, previous gastric surgery and the presence of gastric polyps. Incidence is increasing in Europe The incidence of gastric cancer is decreasing in Europe. Incidence is lower in people with H. pylori infection Risk factors for developing gastric cancer include the presence of H. pylori, blood group A, pernicious anaemia, previous gastric surgery and the presence of gastric polyps. Incidence shows no preference for diets high or low in fresh fruit Fresh fruit and vitamin C may be protective, but there is no consistent evidence to support it. Incidence is higher in those with blood group B o r O Blood group A may be associated with higher incidence, not groups B or O. Gastric cancer in Western Europe often presents in patients over 55 years of age with new -onset dyspepsia/reflux and upper abdominal pain. Other red flags include upper abdominal mass and dysphagia, – these patients should be considered for urgent gastroscopy. Patients may also have nausea, vomiting, anaemia, treatment -resistant dyspepsia or weight loss.

Answer 188

Explanation FAP can present with other extra-colonic connective tissue abnormalities Gardner’s syndrome is a variant of FAP and can present with extra-colonic abnormalities including multiple osteomas, epidermal cysts, desmoid tumours, lipomas and other connective tissue abnormalities. Additionally it is associated with small bowel cancer, thyroid cancer, pancreatic cancer, biliary cancer and hepatoblastoma. FAP is inherited as an autosomal recessive trait FAP is an inherited disease transmitted as an autosomal dominant trait. FAP has an approximate 60% risk of progression to adenocarcinoma In FAP, the risk of progression of an adenomatous polyp to adenocarcinoma is virtually 100%. FAP is diagnosed by computed tomography (CT) scan FAP is normally diagnosed at colonoscopy when a patient is found to have more than 100 polyps alongside a strong family history and genetic testing. The APC gene is an oncogene An oncogene is a gene that is causative in cancer – either through activation or higher expression levels. APC is a tumour suppressor gene – mutation results in inactivation. It is responsible for the production of adenomatous polyposis coli. FAP is an autosomal dominant inherited disease resulting in multiple adenomatous polyps within the colon and a near 100% chance of progression to adenocarcinoma. It is estimated to have an incidence at between 1:7000 to 1:22 000. Less than 1% of colorectal ca ncers is due to FAP. Patients with known FAP should have yearly endoscopic screening at a minimum and will usually require a colectomy at some point in their disease progression (as the number of polyps increases, the risk of cancer increases). Even after colectomy, surveillance is still required at between 6-monthly and 4-yearly testing depending on how much rectal tissue is left.

Answer 189

Explanation They are associated with multiple endocrine neoplasia (MEN) Gastrinoma may occur as one of the MEN syndromes (ie typically MEN 1): MEN type Features MEN1 Parathyroid Pancreas Pituitary MEN2a Parathyroid Phaeochromocytoma Medullary thyroid cancer MEN2b Marfanoid/mucosal neuroma Phaeochromocytoma Medullary thyroid cancer They are malignant in 10% of cases Around 60% of cases are malignant. They occur at extrapancreatic sites in 30% of cases Although gastrin is usually produced by gastric antral G cells, tumours of G cells most commonly originate in the pancreas. Around 10% occur in extrapancreatic sites, eg in the duodenum. They originate from H cells They originate from G cells. They secrete hydrochloric acid G cells secrete gastrin. Gastrin is responsible for stimulating hydrochloric acid secretion from the parietal cells of the stomach. Excess gastrin production results in Zollinger–Ellison syndrome, resulting in widespread peptic ulceration.

Answer 190

Explanation Cancer The risk of developing cancer is higher in ulcerative colitis (UC) than in Crohn’s disease – the main associated risks are duration of disease and extent of disease (ie total colitis is greater than partial colitis). After 10 years of total colitis the risk of cancer is approximately 4–5%. Fistula formation Fistula formation, as well as intra-abdominal or peri-anal abscesses, are a frequent complication of Crohn’s disease. Obstruction Obstruction is a frequent complication of Crohn’s disease. Perianal involvement Perianal problems (fissures, fistulae, skin tags) are much more commonly seen in Crohn’s disease than in UC. Stricture formation Strictures are a frequent complication of Crohn’s disease. Crohn’s disease is a granulomatous inflammatory disorder involving the whole thickness of the bowel wall (any part of the gastrointestinal tract from mouth to anus). Ulcerative colitis is a non - granuloma process that only involves the mucosa. This difference may explain the higher incidence of stricture, obstruction and fistula formation in Crohn’s disease. Perianal problems (fissures, fistulae, skin tags) are much more commonly seen in Crohn’s disease than in UC. UC invariably involves the rectum and extends proximally towards the caecum, and can sometimes cause a ‘backwash ileitis’. Crohn’s disease Ulcerative colitis Segments affected Any part of the alimentary tract from mouth to anus, most commonly the terminal ileum Affects the rectum, extending contiguously proximally a variable amount but limited to the colon Pattern of disease Skip lesions Continuous Macroscopic findings Cobblestones, aphthous and linear ulcers, abscesses, luminal narrowing Pseudopolyps, very friable mucosa, toxic megacolon Microscopic Transmural inflammation, granulomas Submucosal or mucosal findings inflammation, crypt abscesses Common symptoms Abdominal pain, diarrhoea, weight loss, mouth ulcers, perianal disease Bloody diarrhoea, weight loss, abdominal pain Extraintestinal features Perianal disease (fissures, fist ulae, tags, abscesses), mouth ulcers, oral aphthous ulcers, erythema nodosum, arthritis and spondyloarthropathies, uveitis, episcleritis PSC, arthritis and spondyloarthropathies, uveitis, episcleritis

Answer 191

Explanation It may present with rectal bleeding Some cases of Meckel’s diverticulum are asymptomatic, but 1 in 2 contain either heterotopic gastric or pancreatic mucosa. Most symptomatic cases will present before the age of 2 years. Complications of Meckel’s diverticulum include diverticulitis, intussusception, ulceration and gastrointestinal bleeding, intestinal obstruction and perforation. Meckel’s diverticulum, the rule of 2s:  occurs in 2% of the population  2:1 male:female ratio  approximately 2 inches long  found 2 feet from the ileocaecal junction  1 in 2 will contain ectopic tissue (gastric or pancreatic)  only 2% are symptomatic  important cause of rectal bleeding in the under 2s. It is a common cause of malabsorption Most cases of Meckel’s diverticulum are asymptomatic, but 20% contain heterotopic gastric or pancreatic mucosa. Complications of Meckel’s diverticulum include infection/inflammation, intussusception, ulceration and gastrointestinal bleeding, intestinal obstruction and perforation. It is found in over 20% of the general population Meckel’s diverticulum occurs in 2% of the population and affects men twice as often as women. It is invariably found in the jejunum It is classically found in the distal ileum, 60 cm from the ileocaecal valve on the antimesenteric border of the small intestine and is approximately 5 cm long. It may lead to macrocytic anaemia The common causes of macrocytic anaemia include vitamin B12 or folate deficiency, alcohol, liver disease or reticulocytosis – Meckel’s diverticulum does not cause a macrocytic anaemia. Meckel’s diverticulum is a true diverticulum with a mucous membrane and a muscular coat and may be connected to the umbilicus by either a fibrous band or a complete fistula – remnants of the vitellointestinal duct. If a Meckel’s diverticulum is found incidentally, it should be left alone, especially if it is non-inflamed with a wide neck.

Answer 192

Explanation More than 80% of colonic carcinomas arise within adenomatous polyps More than 80% of colorectal cancers arise from pre-existing polyps, which makes the disease suitable for screening. The initial screening test used in the UK is the faecal occult blood test, given to 60–74-year-olds every 2 years. In patients with a positive test or symptoms suggestive of colorectal cancer, endoscopy with colonoscopy or flexible sigmoidoscopy and biopsy is the diagnostic investigation of choice. Irritable bowel syndrome is associated with an increased incidence of colorectal carcinoma Colorectal carcinoma is associated with inflammatory bowel disease, especially ulcerative colitis, rather than irritable bowel syndrome. Left sided colonic tumours usually present with anaemia Right-sided colonic tumours tend to be exophytic and often present with anaemia as the caecum is of a large calibre so rarely obstructs. In contrast, left-sided cancers tend to be stenotic. Left-sided colonic tumours tend to be exophytic Right-sided colonic tumours tend to be exophytic and often present with anaemia as the caecum is of a large calibre so rarely obstructs. In contrast, left -sided cancers tend to be stenotic. The commonest genetic abnormality in colonic carcinoma is p53 The commonest genetic abnormality is in the APC gene – it is a tumour suppressor gene. Mutations in the TP53 gene, which codes for the p53 protein – another tumour suppressor gene – are also common. There are also several syndromes that have a strong association with this cancer [Gardener’s syndrome, hereditary nonpolyposis colorectal cancer (HNPCC) and FAP].

Answer 193

Explanation Hypocalcaemia is relatively common and is caused by fat saponification Acute pancreatitis is an inflammatory process that is caused by the release of pancreatic enzymes from the pancreatic acini. This causes both localised and systemic damage. The release of pancreatic enzymes into the body’s circulation results in fat necrosis and saponification – the free fatty acids released by this process bind calcium and result in systemic hypocalcaemia. Gastrointestinal haemorrhage with resultant haematemesis and melaena is usually the result of rupture of the posterior duodenal artery due to stress Stress-induced gastric erosions frequently occur – these can result in haemorrhage and resultant haematemesis and melaena. This is the most common cause of haemorrhage. Proton pump inhibitors (PPIs) or H 2 antagonists are prophylactically used to prevent stress-induced gastric erosions. Pancreatic pseudocysts are formed in the greater sac of the abdomen Pancreatic pseudocysts are enzyme rich collections, which are formed in the lesser sac of the abdomen following acute and/or chronic pancreatitis. Relative hypoxia in acute pancreatitis is due to multiple sub-clinical pulmonary emboli due to hypercoagulability Hypoxia is usually due to hypo -ventilation due to pain, however, ARDS can also occur due to release of inflammatory mediators. Splenic rupture is a common complication Splenic rupture is a very rare complication of acute pancreatitis. Common complications include: pancreatic pseudocysts, pancreatic abscess, stress-induced gastric erosions with haematemesis or melaena, acute renal failure, toxic psychosis, multiple organ failure, hypocalcaemia and chronic pancreatitis.

Answer 194

Explanation Corrected calcium < 2 mmol/l Prognosis of pancreatitis (Ranson’s criteria) One point is given for each criterion present, severe pancreatitis = three or more points. Age >40 Age > 55 would score a point. Alkaline phosphatase (ALP) > 200 IU/l ALP is not part of the scoring system. Haematocrit <.45 A haematocrit count is not part of the scoring system. Pa (O2 ) < 10 Pa (O2 ) < 8 would score a point. The modified Glasgow criteria enable early diagnosis of severe acute pancreatitis. The following parameters are part of the scoring system:  age > 55  blood glucose > 10 mmol/l – no history of diabetes  white cell count (WCC) > 15.5 × 10 9 /l  lactate dehydrogenase (LDH) > 600 IU/l  aspartate aminotransferase (AST) > 200 U/l  corrected calcium < 2 mmol/l  urea > 16 mmol/l  Pa (O2 ) < 8 kPa (60 mmHg)  albumin < 32 g/l. The mortality per positive criterion:  0–2 < 5% mortality  3–4 20% mortality  5–6 40% mortality  7–8 100% mortality. The modified Glasgow criteria does not include serum amylase, haematocrit or pH.

Answer 195

Explanation Usually presents above the age of 50 Liver cancer incidence is strongly related to age, with the highest incidence rates being in older males and females. In the UK in 2012-2014, on average each year more than 4 in 10 (44%) cases were diagnosed in people aged 75 and over. Women are affected more than men Men are more commonly affected than women, world-wide this varies between 2:1 and 4:1. It is associated with hepatitis A viruses Common viral risk factors include hepatitis B and C viruses (HBV and HCV). In Europe and North America anti-HCV antibodies are present in around 70% of patients with hepatocellular carcinoma. While in countries with endemic hepatitis B 90% of patients with HC C are positive for hepatitis B. Alone, HIV is not a risk factor for HCC although co -infection with HCV and HIV may lead to more rapid progression to HCC. It is associated with type 1 diabetes Type 2 diabetes with poor insulin control may be associated with hepatocellular carcinoma. Serum a-fetoprotein (AFP) levels are in the normal range Serum a-fetoprotein (AFP) levels are usually raised. Patients with cirrhosis due to HBV, HCV, alcohol, primary biliary cirrhosis or haemochromatosis should be offered a 6 -monthly abdominal ultrasound scan and serum AFP test as screening for hepatocellular carcinoma. Clinical features include weight loss, anorexia, fever, a right upper quadrant pain, and ascites. Serum a-fetoprotein is usually raised. Surgical resection is occasionally possible. Chemotherapy and radiotherapy are unhelpful. Survival, except in very selected groups, is seldom more than 6 months.

Answer 196

Explanation Murphy’s sign is right upper quadrant (RUQ) pain on palpation, causing sudden cessation of inspiration and forcing the patient to catch breath Murphy’s sign is an indication of acute cholecystitis. The patient catches breath due to pain on inspiration while the right hypochondrium is deeply palpated, but not when the left hypochondrium is deeply palpated, due to downward movement of the inflamed gall-bladder onto the examining hand during inspiration. Pigment stones area the commonest type of gallstones Cholesterol gallstones are the most common but with haemolytic conditions, such as sickle -cell anaemia, pigment stones are also common. Sickle-cell disease causes largely acalculous cholecystitis Sickle-cell disease results in increased red-cell haemolysis and turnover, leading to a preponderance to develop pigment stones. 80% of gallstones are symptomatic Approximately 70% of gallstones are thought to be asymptomatic and are found on routine ultrasound examination. A common infecting agent in cholecystitis is Salmonella Secondary infection within stagnant bile converts cholelithiasis to cholecystitis. Common organisms are E. coli, Klebsiella, Enterococcus faecalis and Bacteroides.

Answer 197

Understanding Ascites and Its Causes Ascites is the accumulation of fluid in the peritoneal cavity, often associated with liver disease, malignancy, heart failure, or infections. The nature of the fluid can be classified into transudate and exudate based on the serum-ascites albumin gradient (SAAG). This classification helps determine the underlying cause of ascites. 1. Malignancy causing ascites is a transudate This statement is incorrect. Malignant ascites typically presents as an exudate due to increased capillary permeability associated with tumor involvement in the peritoneum. Therefore, malignancy-related ascites usually has a low serum-ascites albumin gradient (<1.1). 2. When associated with oedema this is usually non-pitting This statement is misleading. Edema associated with liver disease and ascites can be either pitting or non-pitting depending on various factors such as the duration and severity of fluid retention. In cases of significant liver dysfunction leading to hypoalbuminemia, edema may present as pitting. 3. A high serum-ascites albumin gradient (>1.1) indicates a transudate such as pancreatitis This statement is incorrect. A high SAAG (>1.1) indicates that the ascitic fluid is likely a transudate, which is commonly seen in conditions like cirrhosis or heart failure rather than pancreatitis specifically, which can lead to exudative ascites. 4. A low serum-ascites albumin gradient (<1.1) indicates an exudate such as hereditary angioedema This statement is also incorrect in its association; while a low SAAG (<1.1) does indicate an exudative process, hereditary angioedema does not typically cause ascites. Exudative causes are more commonly linked to infections (like tuberculosis), malignancies, or inflammatory processes. 5. Spontaneous bacterial peritonitis is due to the introduction of sepsis following an ascitic tap This statement contains some truth but lacks clarity regarding spontaneous bacterial peritonitis (SBP). SBP occurs without any identifiable source of infection and is primarily due to bacterial translocation from the gut flora into the ascitic fluid rather than being directly caused by an invasive procedure like an ascitic tap. Given these evaluations: The correct answer regarding ascites from the options provided would be none of them are entirely accurate, but if we were to select one that aligns closest with common clinical understanding regarding SBP’s pathophysiology without misinterpretation, it would be option 5 concerning SBP’s association with infection risk post-tap. However, since none of these statements accurately reflect established medical knowledge about ascites comprehensively: Answer: None of the statements are correct regarding ascites in their entirety; however, option 5 has elements related to SBP risk post-tap but misrepresents its primary causation mechanism.

Answer 198

Explanation Ascites See overall explanation for tables showing the full scoring system and prognosis depending on score. Aspartate transaminase See overall explanation for tables showing the full scoring system and prognosis depending on score. Bleeding varices See overall explanation for tables showing the full scoring system and prognosis depending on score. Cholesterol See overall explanation for tables showing the full scoring system and prognosis depending on score. Clotting time See overall explanation for tables showing the full scoring system and prognosis depending on score. The Child-Pugh classification takes into account bilirubin level, albumin level, ascites, encephalopathy, and prothrombin time. A B C Bilirubin <34 34-51 >51 Albumin >35 28-35 <28 Ascites None Controlled Refractory Encephalopathy None Minimal Advanced Prothombin <4 4-6 >6 8

Answer 199

Explanation It typically lies about 60 cm from the ileocaecal valve It is classically found in the distal ileum, within 100 cm (typically 60 cm) from the ileocaecal valve on the antimesenteric border of the small intestine and is approximately 5 cm long. Meckel’s diverticulum is a true diverticulum with a mucous membrane and a muscular coat and may be connected to the umbilicus by either a fibrous band or a complete fistula – remnants of the vitellointestinal duct. If a Meckel’s diverticulum is found incidentally, it should be left alone, especially if it is non-inflamed with a wide neck. Meckel’s diverticulum, the rule of 2s:  occurs in 2% of the population  2:1 male:female ratio  approximately 2 inches long  found 2 feet from the ileocaecal junction  1 in 2 will contain ectopic tissue (gastric or pancreatic)  only 2% are symptomatic  important cause of rectal bleeding in the under 2s. It is a partial persistence of the median umbilical ligament A Meckel’s diverticulum is a partial persistence of the vitellointestinal duct and there may be a fibrous connection to the umbilicus. The median umbilical ligament or ‘urachus ’ is a connection between the umbilicus and the bladder. It arises on the mesenteric border of the small bowel Meckel’s diverticulum arises on the antimesenteric border of the small bowel. It is present in 0.2% of individuals It is present in 2% of individuals and affects men twice as often as women. It contains heterotopic pancreatic tissue in 40% of cases Some cases of Meckel’s diverticulum are asymptomatic, but 50% contain heterotopic gastric or pancreatic mucosa. Complications of Meckel’s diverticulum include intussusception, ulceration and gastrointestinal bleeding, intestinal obstruction and perforation.

Answer 200

Explanation It has wide geographical variation in incidence rates and is increasing in frequency in the UK Oesophageal carcinoma in the UK is increasing in incidence. There is a great deal of geographical variation in the incidence, with the highest risk areas being central Asia and South/East Africa. Common risk factors include smoking, alcohol, ingestion of caustic agent s (including very hot drinks), age, obesity and previous radiotherapy. Squamous-cell carcinomas of the oesophagus usually occur in the upper two -thirds of the oesophagus and are associated with GORD If found in the lower one-third of the oesophagus, it is usually of the adenocarcinoma type and associated with gastro -oesophageal reflux disease (GORD). If found in the upper two -thirds of the oesophagus is of similar origin as head and neck cancers and is of squamous -cell origin. This type, however, is usually associated with smoking not GORD as the above answer states. The development of a hoarse or husky voice is a concerning feature likely to be due to direct invasion of the aryepiglottic folds A hoarse voice is a worrying feature but is usually due to involvement of the recurrent laryngeal nerve. Palliation of symptoms is seldom necessary as most patients die soon after developing dysphagia Palliation is an important aim of all treatment for oesophageal cancers when cure is not possible. Overall survival for oesophageal cancer is 40% at 1 year, 15% at 5 years (cancer research UK statistics). However, survival varies by type (squamous-cell carcinoma or adenocarcinoma) and by stage of presentation. Early cancers may be fully resectable with oesophagectomy or endoscopic mucosal resection for very early cancer. Adjuvant and neoadjuvant radiotherapy and chemotherapy are also used in oesophageal cancer. Diagnosis is usually established by a barium swallow alone Diagnosis may be suggested by a barium swallow but definitive diagnosis requires histology obtained via an oesophago -gastro- duodenoscopy (OGD).

Answer 201

Explanation The urea breath test The urea breath test detects radiolabelled carbon dioxide in the breath after ingesting radiolabelled urea (sensitivity 95%, specificity 96%). Culture of biopsy material Culture of biopsies may yield the presence of H. pylori, but this is not routinely used McNemar’s test McNemar’s test is a non-parametrical statistical test and nothing to do with H. pylori. The biopsy urease test Biopsy of the stomach wall is the basis of the urease test (‘Clo -test’), which takes up to 30 min to get a result and depends on the presence of urease in the bacterium to alter the substrate from orange to pink. Sensitivity is the highest of the presented options (98%), but it is not highly specific (82%). Serology/stool testing Serology testing is used, but serological testing (sensitivity 92%, specificity 83%) performs less well when compared with breath testing, which is the most sensitive and specific (sensitivity 95%, specificity 96%) and stool testing (sensitivity 95%, specificity 94%)

Answer 202

Explanation Barrett's oesophagus Barrett’s oesophagus is considered a pre-malignant lesion associated with a risk of 6–14% of developing oesophageal adenocarcinoma and requires regular endoscopic surveillance. T he relative risk of oesophageal cancer is approximately 11. Human papillomavirus (HPV) infection The relative risk of oesophageal squamous-cell carcinoma is between 2.4 and 3.6 in human papillomavirus (HPV) infected patients. Alcohol Alcohol is a recognised risk factor for squamous carcinoma, the risk increases with volume drunk with relative risk of between 1.8–7.4. Gastro-oesophageal reflux disease The relative risk of adenocarcinoma is between 4.9 for patients who have weekly symptoms, to 7.4 for patient s who have daily symptoms. Helicobacter pylori infection This infection is associated with gastric cancer rather than oesophageal cancer. The most common presenting symptom of oesophageal cancer is dysphagia, usually this will progressively worsening and symptoms will start with dysphagia to food and progress on to dysphagia for liquids. Cancer in the distal third of the oesophagus is most frequently adenocarcinoma, which is most commonly associated with gastro -oesophageal reflux disease and especially Barrett’s oesophagus. Cancers of the upper two -thirds of the oesophagus are classically squamous-cell carcinomas. 884 Intussusception is much more common in the paediatric population. Often a lesion in the bowel will cause the pathological process to take place.

Answer 203

Explanation Hypertrophic Peyer’s patch Peyer’s patches in the ileum are the pathological lead patch in up to 90% of cases. Dance’s sign Dance’s sign, (a feeling of emptiness on palpation), with viscera absent in the right lower quadrant on abdominal X-ray is seen in 15% of cases. It is not, however, a ‘lead point’ in intussusception. Intraluminal haematoma An intraluminal haematoma in Henoch–Schönlein purpura may trigger intussusception. Meckel’s diverticulum Meckel’s diverticulum and polyps are identified as a pathological lead point in 10% of cases. Polyps Meckel’s diverticulum and polyps are identified as a pathological lead point in 10% of cases. Intussusception is a condition where a part of the bowel, normally small bowel, telescopes inside an adjacent part of the bowel. It is most common in infants aged 4 months to 1 year, with peak incidence between 6–9 months. Risk factors, aside from age, include previous intussusception, or family history of the condition, and intestinal malrotation. It presents with abdominal pain, ‘redcurrant jelly’ stool and signs of obstruction and sepsis. Diagnosis can be made on ultrasound scan (USS) or on air or contrast enema. The enema can serve a dual purpose to also decompress the intussuscepted segment. If this fails surgery may be required. Pathologically the theory is th at a ‘lead point’ is usually to blame that instigates the telescoping – it is thought that up to 90% of cases are as a result of Peyer’s patches.

Answer 204

Explanation There is a congenital ganglion absence in the rectum In Hirschsprung’s disease there is a defective neural crest -cell migration resulting in a congenital absence of the ganglia that normally make up Auerbach (myenteric) plexus and Meissner (submucosal) plexus to part of the colon. The result of this absence is increased tone in the affected part of the colon, and an absence of appropriate peristalsis that causes a functional (rather than mechanical) obstruction. There will be dilation of the affected segment Dilatation occurs proximal to the affected segment. The affected segment is hypertonic and therefore stenotic so faeces accumulate proximal to this. This affects both sexes equally Hirschsprung’s disease occurs in 1 in 5000 births and has an M:F ratio of 5:1. This is diagnosed by cold-cup rectal biopsy Suction biopsy of the narrowed segment is first line, this is examined for absence of Auerbach and Meissner plexus. Full-thickness rectal biopsy is required if suction biopsy is inconclusive. This usually presents in patients greater than 10-years of age Most commonly Hirschsprung’s disease is diagnosed shortly after birth because of failure to pass meconium within 48 h of deliver y. Other symptoms can include signs of obstruction such as abdominal distension and vomiting. Additionally diagnosis can be delayed, presenting later in childhood with chronic constipation.

Answer 205

Explanation Wilson’s disease In Wilson’s disease, the presence of Kayser –Fleischer rings indicates neurological impairment. It consists of copper deposition in the cornea and may be seen as a greenish or golden brown ring around the cornea on slit lamp examination. Symptoms mostly relate to deposition of copper in the liver (causing liver disease) and brain (causing neuropsychiatric symptoms, such as parkinsonism due to deposition in the basal ganglia). Autoimmune hepatitis Autoimmune hepatitis has no specific associat ed eye signs, it can present as an acute or chronic hepatitis. Sclerosing cholangitis This condition is frequently associated with inflammatory bowel disease, especially ulcerative colitis. It may present before or after diagnosis of inflammatory bowel disease. Symptoms are mostly related to liver disease, there are no specific eye signs. Primary biliary cirrhosis (PBC) Patients with PBC frequently develop xerostomia and dry eyes. It typically presents in middle - aged women with intense itching and signs of liver disease such as jaundice. Haemochromatosis There are no specific eye signs associated with this condition. Presentation can include liver disease, cardiac failure, arthritis, diabetes, tray-bronze skin and other endocrine complaints.

Answer 206

Explanation Subphrenic abscess Subphrenic abscess usually arises 3 to 6 weeks following abdominal surgery, mainly to the biliary tract, duodenum or stomach, or following a perforated viscus or anastomotic leakage. The subphrenic space is in direct contact with the para-colic gutter thereby allowing peritoneal contamination such as bile, blood or bowel contents to spread. Subphrenic abscess is right -sided in about 50%, left -sided in 25% and bilateral in 25% of patients. Clinical features include pyrexia with chills and rigors, anorexia, loss of appetite and loss of weight. Diaphragmatic irritation may affect the lung, resulting in chest pain, dyspnoea and non - productive cough. Basal atelectasis, pneumonia and pleural effusion are recognised complications of this condition. Additionally, diaphragmatic irritation can cause referred pain to the shoulder because the phrenic nerve (which innervates the diaphragm) shares nerve roots with the dermatomes overlying the shoulder (ie roots C3 –5). Ultrasound scan is the investigation of choice to diagnose subphrenic abscess, and, if an abscess is identified, ultrasound guided percutaneous drainage catheter may be placed at the same time. Emphysema of right lung Pulmonary emphysema is a chronic lung condition that, along with chronic bronchitis, is now more commonly known clinically as chronic obstructive pulmonary disease (COPD). In emphysema there is dilation of the airways distal to the terminal bronchioles due to destruction of elastase within the supporting connective tissue of the distal airways, most commonly it is associated with smoking although a less predisposing factor is alpha 1 -antitrypsin deficiency. Patients with chronic obstructive pulmonary disease (COPD) are predisposed to lower respiratory tract infections which would explain the shortness of breath, fevers and c hest X-ray changes, but would not normally cause RUQ tenderness with pain radiating to the shoulder. Acute pancreatitis Acute pancreatitis is an important differential of the acute abdomen, however, this patient’s recent surgery and confirmed appendicitis, combined with atypical signs for pancreatitis (ie RUQ pain) means this diagnosis is not the most likely. It rarely presents with rigors. Sclerosing cholangitis Sclerosing cholangitis is a chronic inflammatory condition, usually found in the presence of inflammatory bowel disease. It can lead to chronic liver disease through obstruction of the biliary ducts. It is not a likely diagnosis in this acute scenario especially without evidence of liver disease (eg jaundice). Pyonephrosis Pyonephrosis is a collection within the renal pelvis. It is a recognised complication of pyelonephritis, renal stones or hydronephrosis but can also occur as a primary condition. You would expect the patient’s pain to be over the renal angle more that the right hypochondrium, urinary symptoms may be present, and chest signs would not be typical.

Answer 207

Explanation Mesenteric infarction (Ischaemic bowel disease) The history, signs and symptoms are classical of mesenteric infarction, which is part of the spectrum of ischaemic bowel disease. While ischaemic bowel disease is a spectrum of acute and chronic conditions resulting in inadequate blood flow to the bowel (either large or small), mesenteric infarction specifically implies an obstruction to blood flow of the small bowel (which is supplied by the mesenteric vessels) that has resulted in cell death. The risk factors include age, atrial fibrillation, previous myocardial infarction, heart failure and thrombophilia – the ischaemia then caused by an embolic event. Mesenteric infarction typically presents with persistent and generalised abdominal pain. Vomiting may or may not be present. Some patients may pre sent with shock, with the shock being out of proportion to the clinical symptoms. The infarcted bowel may shed the ‘non-viable mucosa’, which mixed with mucus, results in dark-coloured (also known as plum-coloured) stools. The inflammatory markers such as the white cell count and C- reactive protein may be elevated. Arterial blood gas analysis is a very useful investigation, which may reveal a metabolic acidosis. This condition is a surgical emergency as the patient rapidly become septic and may die from septic shock unless the infarcted bowel (‘dead gut’) is removed. Sigmoid volvulus This condition typically presents with abdominal distension and failure to pass stool or flatus (absolute constipation), lower abdominal pain is also a frequent symptom. Their a bdomen will be clinically distended but may not be tender. Complications include ischaemia of the section affected, perforation and peritonitis. Risk factors include being elderly, chronic constipation and male gender. Acute small bowel obstruction Acute small bowel obstruction normally presents with colicky abdominal pain, nausea and vomiting failure to pass stool/flatus occurring after this as the obstruction may be relatively proximal. Mostly commonly it is secondary to adhesions, hernias or malignancy. Other causes of small bowel obstruction include Crohn’s disease, volvulus, and foreign bodies (including gallstone ileus and swallowed foreign bodies). Toxic megacolon Toxic megacolon presents as a complication to conditions such as inflammatory bowel dise ase or Clostridium difficile infection most commonly. It presents with severe abdominal pain, distention and signs of sepsis. With no antecedent history of a causative condition this option is not the most likely. Leaking abdominal aortic aneurysm A leaking abdominal aortic aneurysm may present acutely with haemorrhagic shock, or subacutely less commonly. Additionally the rupture may be contained within the retroperitoneum or uncontained – the latter allowing for much greater and faster blood loss. Classic signs include abdominal pain, back pain, hypotension and a palpable expansile mass in the abdomen. This diagnosis could account for the patient’s relatively shocked state, but does not explain the fever or dark stool.

Answer 208

Colonic carcinoma Elderly patients with per rectal bleeding, change in bowel habit, and weight loss should be considered to have colonic cancer unless proven otherwise. Toxic megacolon Toxic megacolon normally presents secondary to a predisposing condition, such as ulcerative colitis or C. difficile infection. It is an acute presentation, with abdominal pain and distension and signs of sepsis. Acute colonic pseudo-obstruction The chronicity of the history makes acute colonic pseudo -obstruction unlikely. Sigmoid volvulus Sigmoid volvulus usually presents with a rapid onset abdominal distension and absolute constipation. The chronic history to this presentation makes a sigmoid volvulus unlikely, it would also not explain the per rectum (PR) bleeding nor the weight loss. Diverticular disease While diverticular disease can explain the patient’s change in bowel habit and PR bleeding, it does not explain the patient’s weight loss. The clinical presentation of patients with colonic malignancy depends on the site of the tumour. Right-sided colonic carcinoma commonly presents with anaemia, tiredness, malaise, pallor and loss of weight, while the left -sided colonic carcinoma presents with change in the bowel habits, bleeding per rectum and intestinal obstruction. Rectal carcinoma, in addition to the features seen in left-sided colonic carcinoma, is associated with a sense of incomplete evacuation of the bowel (tenesmus). Increase in age is a risk factor for developing colonic cancer. The other risk factors, among others, include a family history of colon cancer, familial adenomatous polyposis, diet rich in red meat and long standing ulcerative colitis or Crohn’s disease. The investigation of choice for suspected colonic malignancy is a colonoscopy with biopsy of suspicious lesions. If this is not possible, usually due to patient’s lack of fitness for the examination, then flexible sigmoidoscopy or computed tomography (CT) colonoscopy is usually the next line. Carcinoembryonic antigen (CEA) is the commonly used tumour marker to diagnose colonic malignancy and subsequently to assess the progress, including recurrence. Obviously, in a case of acute obstruction due to suspected malignancy a different initial set of investigations will be required, likely to include basic bloods and plain abd ominal X-ray (AXR), with CT scan likely required acutely if surgery is contemplated. Dukes’ classification for colorectal cancers is useful to be aware of, however, in clinical practice the TNM classification is now more frequently used. Classification Disease extent Duke A Limited to muscular propria Duke B Extending beyond muscularis propria Duke C Lymph node involvement Duke D Distant Metastatic spread

Answer 209

Explanation Gastrinoma Gastrinomas, which occur primarily in the pancreas and duodenum, are malignant in nearly two - thirds of cases. The patients may present with upper abdominal/epigastric pain and vomiting; the vomitus may be ‘coffee-ground’ due to bleeding from the ulcers. Ninety per cent of patients with gastrinomas develop peptic ulceration due to excess gastrin release by the tumour – gastrin stimulates gastric acid hypersection, which causes ulceration. Gastrinomas may eit her arise sporadically or as part of Zollinger–Ellison syndrome (peptic ulceration, gastric acid hypersecretion and islet -cell tumour of the pancreas). Sporadic Zollinger –Ellison occurs most frequently in the fifth decade of life. Approximately 20% of patients with Zollinger–Ellison syndrome have MEN type I syndrome. An elevated basal gastric acid output >15 mEq/h and a serum gastrin >1000 pg/ml are suggestive of a gastrinoma. If it is difficult to make a diagnosis, a secretin stimulation test may be indicated. Lesions are localised by somatostatin-receptor scintography. A CT scan may be indicated to exclude metastases. The treatment of this condition is either conservative (high dose proton pump inhibitors) or surgical. Surgical resection may be aided by intra-operative ultrasound and/or intra-operative endoscopy. Carcinoid tumour This is a neuroendocrine tumour most commonly found in the small bowel. It can cause local symptoms (eg in the bowel it can cause bowel obstruction, bleeding or diarrhoea), and sym ptoms as a result of release of hormones such as serotonin into the bloodstream (carcinoid syndrome – diarrhoea, abdominal pain, flushing, tachycardia, wheeze). They can be sporadic, but are also part of MEN-1. Diagnosis is by 24-h urinary collection to detect unusually high levels of urinary carcinoid breakdown products. Somatostatinoma This is a tumour of the delta cells (the cells responsible for production of somatostatin) of the pancreas. The clinical result of this is a result of the inhibitory actions of somatostatin on various pancreatic and gastrointestinal hormones: suppression of insulin – diabetes, suppression of CCK and secretin – steatorrhoea and gallstones, suppression of gastrin – hypochlorhydria. Vasoactive intestinal peptide tumour VIPomas develop from pancreatic islet cells. Release of VIP results in sometimes profound watery diarrhoea, hypokalaemia and associated symptoms, abdominal pain, weight loss. ACTH secreting tumour ACTH tumours are normally pituitary tumours, however, exogenous ACT H production can result from other tumours (notably certain lung cancers). Excess ACTH production results in excess stimulation of cortisol production in the adrenals and therefore Cushing’s syndrome.

Answer 210

Step-by-Step Analysis of the Symptoms and Diagnosis Patient Presentation: The patient is a 28-year-old female hair stylist presenting with a 3-month history of: Crampy lower abdominal pain Diarrhoea (12–15 times/day) Mouth ulcers Loss of appetite Significant weight loss (nearly a stone) Physical Examination Findings: Mildly tender mass over the right iliac fossa Presence of abscesses with sinus formation in the perianal region Differential Diagnosis Consideration: Pelvic Inflammatory Disease (PID): Typically presents with lower abdominal pain, fever, and abnormal vaginal discharge. Less likely due to the absence of fever and specific gastrointestinal symptoms. Pseudomembranous Colitis: Often caused by Clostridium difficile infection, leading to diarrhea and abdominal pain. Usually associated with recent antibiotic use, which is not mentioned in this case. Ulcerative Colitis: A form of inflammatory bowel disease (IBD) characterized by continuous inflammation of the colon. Symptoms include bloody diarrhea, abdominal pain, and urgency but does not typically present with perianal abscesses or sinus formation. Crohn’s Disease: Another type of IBD that can affect any part of the gastrointestinal tract. Commonly presents with abdominal pain, diarrhea (which may be bloody), weight loss, and complications such as strictures or fistulas. The presence of perianal abscesses is particularly indicative of Crohn’s disease. Carcinoma of the Colon: Generally presents later in life with changes in bowel habits, weight loss, and possibly obstruction. Less likely given the patient’s age and symptom profile. Conclusion: Considering all symptoms presented—particularly the combination of crampy abdominal pain, frequent diarrhea, mouth ulcers, significant weight loss, and especially the presence of perianal abscesses—the most fitting diagnosis for this patient is Crohn’s disease. This condition aligns well with her clinical presentation and physical examination findings. Thus, based on this thorough analysis: Answer: Crohn’s disease

Answer 211

 cholecystocholedochal fistula formation due to direct pressure necrosis of adjacent duct walls from large impacted stones. Patients may present with pain over the right upper quadrant of the abdomen, vomiting, fever, recurrent cholangitis, cholecystitis or pancreatitis. Pale stools and dark urine result from obstruction of the flow of bile into the intestine. Treatment of this condition is exploration of the common bile duct by either open or laparoscopic cholecystectomy and placement of a T-tube. Carcinoma of the head of the pancreas This is the commonest malignant cause of obstructive jaundice classically causing ‘painless jaundice’ and presenting late. The acute history and tenderness is not typical for this presentation, additionally the imaging findings are not in keeping with this diagnosis. Cholangiocarcinoma This is a relatively uncommon malignant cause of obstructive jaundice. The acute history and tenderness is not typical for this presentation, additionally the imag ing findings are not in keeping with this diagnosis. Hepatocellular carcinoma Hepatocellular carcinoma (HCC) does not typically cause obstructive jaundice. In the UK it is normally found in patient’s with underlying liver disease or cirrhosis, for example due to hepatitis B, C or alcohol. Aflatoxin ingestion is a notable cause in South-East Asia and sub- Saharan Africa – this is a toxin produced by fungal growth in certain grains. Presentation of HCC may be on routine screening of patients with known liver d isease, with local physical symptoms such as right upper quadrant pain, or with signs of liver failure – either due to decompensation of underlying liver disease or massive infiltration of the liver by the carcinoma cells. Carcinoma of the ampulla of Vater This is a rare cancer arising from the ampulla of Vater. It most commonly presents with obstructive jaundice, however, the acute history and tenderness is not typical for this presentation, additionally the imaging findings are not in keeping with this diagnosis.

Answer 212

Explanation Alcoholic liver cirrhosis Alcoholic liver cirrhosis can cause portal hypertension; which causes the stigmata this patient presents with. Portal hypertension is defined as an increase in the portal vein pressure of more than 10 mmHg (the normal portal vein pressure is in the range of 5 –10 mmHg). Among other causes, cirrhosis of the liver is one of the important causes of portal hyperte nsion and currently accounts for up to 90% of cases in the UK. As a result of the portal hypertension collateral channels develop between the portal system and systemic circulation – common sites for this include the lower end of oesophagus (resulting in o esophageal varices), distal rectum, and anterior abdominal wall (resulting in dilated tortuous veins in the anterior abdominal wall known as caput medusae). Bleeding from varies can be profuse and life-threatening – bleeding from oesophageal varies is part icularly common particularly oesophageal varices leading to haematemesis and/or melaena. Treatment requires urgent resuscitation, definitive management is usually endoscopic. Some of the signs and symptoms of portal hypertension include abdominal pain, ascites, jaundice, splenomegaly and signs of cirrhosis (such as spider naevi, gynaecomastia, palmar erythema and testicular atrophy). Chronic pancreatitis Chronic pancreatitis can present either due to chronic insufficiency of it is exocrine function (causing steatorrhoea, fat-soluble vitamin deficiency and weight loss), endocrine function (most notably causing insulin-dependent diabetes mellitus) or due to distinct episodes of acute -on- chronic inflammation presenting with severe epigastric abdominal pain and often vomiting. Alcohol is the commonest cause of this condition in the UK. Hepatocellular carcinoma (HCC) In the UK this condition is normally found in patient’s with underlying liver disease or cirrhosis, for example due to hepatitis B, C or alcohol. Aflatoxin ingestion is a notable cause in South-East Asia and sub-Saharan Africa – this is a toxin produced by fungal growth in certain grains. Presentation of HCC may be on routine screening of patients with known liver disease, with local physical symptoms such as right upper quadrant pain, or with signs of liver failure – either due to decompensation of underlying liver disease or massive infiltration of the liver by the carcinoma cells. Amoebic hepatitis Entamoeba histolytica can cause localised abscesses or a diffuse hepatitis. Presentation normally includes right upper quadrant tenderness and hepatomegaly, fever, and possibly jaundice. Bloods will show evidence of hepatitis. Liver infection will normally follow an episode of intestinal amebiasis/amoebic d ysentery. Risk factors for this condition include old age, recent tropical travel and immunosuppression (including chronic alcohol use, steroids, HIV, etc.). Myeloproliferative disorder Myeloproliferative disorders encompass chronic myeloid leukaemia (CML) , essential thrombocythaemia, polycythaemia (rubra) vera and myelofibrosis. They can all cause hepatosplenomegaly and portal hypertension (which explains this patient’s presentation) – however, in a patient drinking as much alcohol as this portal hypertens ion caused by liver cirrhosis is the most likely cause.

Answer 213

Explanation Chronic cholecystitis Chronic cholecystitis is associated with a fibrotic thick walled gall-bladder. Within the thickened wall are Aschoff–Rokitansky sinuses, mucosal herniations often containing inspissated bile. Acute cholecystitis Acute cholecystitis is associated with increased vascular permeability and infiltration with acute inflammatory cells. Cholesterosis of the gall-bladder (strawberry gall-bladder) Cholesterol-laden macrophages in the lamina propria of the gall-bladder mucosa are a feature of cholesterosis. Mucocele of the gall-bladder Mucocele of the gall-bladder normally occurs in a thin walled non-inflamed gall-bladder. Xanthogranulomatous cholecystitis Xanthogranulomatous cholecystitis is a rare form of chronic cholecystitis characterised by huge numbers of lipid-laden macrophages and giant -cells. Xanthogranulomatous cholecystitis can easily be mistaken for carcinoma.

Answer 214

Explanation Primary sclerosing cholangitis Primary sclerosing cholangitis is far more common in ulcerative colitis than in Crohn’sdisease. It is characterised by a progressive fibrous inf lammatory reaction within the biliary tree leading to irregularity with multiple stenosis and biliary obstruction. There is no apparent relationship between the duration or severity of ulcerative colitis and ultimate progression to liver failure. Ankylosing spondylitis Arthropathy and ankylosing spondylitis are both features of ulcerative colitis and Crohn’s disease. Ankylosing spondylitis is slightly more common in ulcerative colitis. Arthropathy Arthropathy and ankylosing spondylitis are both features of ulcerative colitis and Crohn’s disease. Erythema nodosum Erythema nodosum is the commonest cutaneous manifestation of inflammatory bowel disease and occurs slightly more commonly in Crohn’s disease. Pyoderma gangrenosum Pyoderma gangrenosum is slightly more prevalent in ulcerative colitis than Crohn’s disease, however, primary sclerosing cholangitis is far more common still in ulcerative colitis. The following table summarises several key differences between ulcerative colitis and Crohn’s disease. Crohn’s disease Ulcerative colitis Segments affected Any part of the alimentary tract from mouth to anus, most commonly the terminal ileum Affects the rectum, extending contiguously proximally a variable amount but limited to the colon Pattern of disease Skip lesions Continuous Macroscopic findings Cobblestones, aphthous and linear ulcers, abscesses, luminal narrowing Pseudopolyps, very friable mucosa, toxic megacolon Microscopic findings Transmural inflammation, granulomas Submucosal or mucosal inflammation, crypt abscesses Common symptoms Abdominal pain, diarrhoea, weight loss, mouth ulcers, perianal disease Bloody diarrhoea, weight loss, abdominal pain Extraintestinal features Perianal disease (fissures, fistulae, tags, abscesses), mouth ulcers, oral aphthous ulcers, erythema nodosum, arthritis and spondyloarthropathies, uveitis, episcleritis PSC, pyoderma gangrenosum, arthritis and spondyloarthropathies, uveitis, episcleritis

Answer 215

Explanation Anaemia of chronic disease The serum iron, iron-binding capacity and saturation are all low, but there is plenty of storage iron that is not being utilised so ferritin is normal. These symptoms are typical of anaemia of chronic disease – you would also expect to find a normal mean corpuscular volume (MCV) (normocytic). Autoimmune haemolytic anaemia In haemolytic anaemia the haemolysed cells release haemoglobin that is usually not lost from the body and is recycled, so the iron studies are usually normal. The patient’s MCV will normally be increased due to reticulocytosis (macrocytic), while LDH and bilirubin will be increased and haptoglobin decreased. Chronic blood loss Chronic blood loss can lead to iron deficiency because of the loss of iron, with a low serum iron, high TIBC and low ferritin. The MCV is typically decreased (microcytic). Malabsorption Malabsorption, particularly in disease processes involving the duodenum, can occasionally explain iron deficiency anaemia, which has a high TIBC and low ferritin. Malabsorption involving the distal ileum can produce a megalobla stic anaemia through malabsorption of vitamin B 12 (macrocytic). Vitamin B 12 deficiency Vitamin B 12 and folate deficiencies lead to a megaloblastic anaemia that is not associated with abnormalities in iron metabolism. The bone marrow contains megaloblastic cells, while peripheral blood contains large red blood cells (macrocytosis) and hypersegmented neutrophils. The following table explains the expected results of iron studies in several conditions: Iron TIBC TIBC saturation Ferritin MCV Iron deficiency Low High Low Low Decreased Anaemia of chronic disease Low Low Low Normal Normal Acute phase response Low Low Low High Normal Haemochromatosis/iron overload High Low High High Normal

Answer 216

Explanation Increased neutrophil segmentation This is a sign of megaloblastic anaemia, known as hypersegmented neutrophils, which is a symptom of atrophic gastritis due to vitamin B-12 deficiency. Other signs include macrocytosis (high MCV), and megaloblasts within the bone marrow. Decreased mean corpuscular volume in the red blood cells Decreased microcytosis (MCV) is classic of iron deficiency anaemia, as well as thalassaemia and sideroblastic anaemia. Decreased serum ferritin Decreased serum ferritin represents a lack of iron stores in the body, for example in iron deficiency anaemia. Decreased serum folate Folate deficiency leads to a megaloblastic anaemia. Its absorption is not affected by atrophic gastritis. Increased reticulocyte count Increased reticulocyte count is a classic sign of haemolytic anaemia.

Answer 217

Explanation Hereditary non-polyposis colorectal cancer Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited condition – there are various genes that may be involved but they are all characteristically involved in DNA mismatch repair. Colonic tumours associated with HNPCC tend to have certain distinguishing pathological features. They occur on average 20 years before the peak incidence of sporadic tumours and are frequently synchronous and metachronous with a predilection for the proximal colon. They tend to be mucinous, poorly differentiated and ‘signet -ring’ in appearance. Ovarian cancer is associated with HNPCC along with cancers of the endometrium and stomach. Cowden’s syndrome This is an autosomal-dominant condition associated with multiple hamartomas (especially in the breast and thyroid tissue, skin and mucosal membranes), and an incr eased incidence of certain cancers (breast and endometrial in women, as well as thyroid and renal cancers). Familial adenomatous polyposis This condition is inherited, resulting in the development of 100s of polyps in the large bowel, with an associated increased risk of colorectal cancer. Additionally, patients are at increased risk of other cancers including pancreatic and stomach, and have other characteristic findings such as osteomata, sebaceous cysts and fibromas. A specific collection of signs/sympto ms in familial adenomatous polyposis (FAP) is known as Gardner syndrome. Juvenile polyposis Juvenile polyposis is a genetic condition in which multiple hamartomas develop within the gastro intestinal tract (GI) tract with an associated increased risk in ca ncer of the GI tract (from the stomach to rectum). Peutz-Jeghers syndrome This autosomal-dominant condition is characterised by multiple patches of hyperpigmentation on the lips/oral mucosa and hands and feet, and hamartomas within the GI tract. Patients a re also at increased risk of cancer in the pancreas, liver and lung, in men also in the testicles and in women the breast, uterus and ovaries.

Answer 218

Explanation Development of chronic hepatitis C In total, 50–80% of those with acute hepatitis C will develop a chronic infection. Complete recovery In total, 25–50% of patients with acute hepatitis C will completely clear the virus and therefore make a complete recovery. End stage liver disease In total, 20% of those individuals affected by chronic hepatitis C will develop progressive cirrhosis and resultant end-stage liver failure. Additionally, hepatocellular carcinoma occurs in 1–4% of those with associated cirrhosis per year. Transmission to her monogamous partner Transmission to monogamous partners and vertical transmission is uncommon and accounts for the minority of new cases of hepatitis C virus infection. Hepatitis C virus is transmitted by parenteral or per mucosal exposure to infected blood or body fluids. Many patients have a history of intravenous drug abuse or transmission of blood products before the implementation of antihepatitis C virus screening of blood donors in 1992. Vertical transmission to potential children Transmission to monogamous partners and vertical transmission is uncommon and accounts for the minority of new cases of hepatitis C virus infection. Hepatitis C virus is transmitted by parenteral or per mucosal exposure to infected blood or body fluids. Many patients have a history of intravenous drug abuse or transmission of blood products before the implementation of antihepatitis C virus screening of blood donors in 1992. Hepatitis C virus has risk factors for infection in the UK patient population including intravenous drug use with sharing of paraphernalia, blood product transfusion (before screening for HCV in 1992), tattoos or piercings, while sexual and vertical transmission are also routes they are less common. Acute hepatitis C is defined as being the first 6 months of infection after the incubation period, while chronic hepatitis C is an infection longer than this period. Most patients are asymptomatic during this period – however, testing for hepatitis C should be considered in patients with clinical features of hepatitis (RUQ pain, jaundice, flu -like symptoms, diarrhoea and vomiting), risk factors, or deranged liver function tests. The presence of HCV antibodies show whether a patient has ever been infected with HCV, while the presence of HCV RNA shows an active infection.

Answer 219

Explanation Most anal malignancies are squamous cell carcinomas Of anal cancers, 80% of them are squamous-cell carcinomas. Rectal bleeding is the most common initial symptom (45% of cases); 30% of patients complain of pain or sensation of a mass. First-line treatment is by radical surgery Anal carcinoma is relatively radiosensitive. Presently, combination radiotherapy and chemotherapy [fluorouracil (5-FU) ± mitomycin or 5-FU + cisplatin] is used as initial standard first-line treatment. Abdominoperineal (AP) resection is reserved for recurrent or resistant tumours or in combination with neoadjuvant chemo -radiotherapy. It accounts for 50% of anorectal malignancies Anal cancers account for approximately 10% of anorectal ma lignancies. Perianal papilloma is not related to the development of anal cancer Perianal papillomas have been shown to predispose to the development of anal cancer. The human papillomavirus (usually type 16) may cause papillomas/intraepithelial neoplasia, which with time progresses to anal carcinoma. This virus is found in approximately 70% of patients. Other risk factors for anal carcinoma include a history of cervical or vaginal cancer, history of sexually transmitted disease and immunosuppression following solid organ transplantation. Tumours above the dentate line spread to the para-aortic lymph nodes The nodal metastatic locations depend on the lymphatic drainage, which is dependent on where the anal cancer originates: above the dentate line, flows to t he perirectal and internal iliac nodes; below the dentate line, drainage is through the inguinal and femoral nodes. The most common site of distal metastasis is the liver.

Answer 220

Explanation It has a palpable mass on digital rectal examination in over 60% of cases of rectal tumours Colorectal cancer presents as a palpable rectal mass in 60% of cases of rectal tumours. Other common symptoms of a rectal cancer include peri-rectal (PR) bleeding, change in bowel habit, tenesmus, or abdominal discomfort. It is associated with a high fibre, low fat diet The opposite is true, a high fat and low fibre diet predisposes to colorectal c arcinoma. Other risk factors include diet high in red/processed meat, obesity, increasing age, alcohol and tobacco use. Additionally other conditions such as inflammatory bowel disease, and inherited conditions such as familial adenomatous polyposis syndro me and hereditary non-polyposis colorectal cancer (HNPCC) syndrome are significant risk factors. It is associated primarily with Krukenberg’s tumours Krukenberg’s tumours are malignant metastases within the ovaries – their primary site is normally gastrointestinal (GI), primarily it is associated with stomach carcinomas spreading to ovaries. It is best treated by abdominal-perineal resection if the tumour is up to 15 cm from the anal canal Abdominal–perineal resections are used for low rectal tumours, where tumours are within 8 cm from the anal canal. Left -sided tumours above this point may undergo left hemi-colectomy, while transverse and right -sided hemi-colectomies may be used in these respective areas. Right - sided hemi-colectomy is also the operation of choice for caecal tumours. Radiotherapy is frequently used in rectal cancers too – either as neoadjuvant or adjuvant therapy, but not commonly in other cancers of the colon. Chemotherapy may be used in all sites of colorectal cancer, depending on type/stage. It is found in the rectum in 10% of cases Approximately 45% of colorectal tumours are found in the rectum. It is useful to be aware of the Dukes’ staging system for colorectal cancer (although this system has largely been replaced by the TNM staging system clinically it is a frequent exam question!). Please see the following link for a comprehensive description of colorectal cancer staging by the American Joint Committee on Cancer (AJCC, 7th edition). Modified Astler –Coller staging system:  Stage A: Limited to mucosa  Stage B1: Extending into the muscularis propria but not penetrating through it; nodes are not involved.  Stage B2: Penetrating through the muscularis propria; nodes are not involved.  Stage C1: Extending into the muscularis propria but not penet rating through it. Nodes are involved.  Stage C2: Penetrating through the muscularis propria. Nodes are involved.  Stage D: Distant metastatic spread.

Answer 221

Explanation Ulcerative colitis There is malignant potential in ulcerative colitis – after 10 years the risk is around 2%, then 8% at 20 years and 18% at 30 years. Those individuals with ulcerative colitis for 10 years or longer are offered surveillance at between 1–5-yearly intervals depending on whether they are deemed low, intermediate or high risk of developing colorectal cancer. Haemorrhoids Haemorrhoids are swollen or inflamed vascular structures within the anal canal. They can present with pain, itching and per rectal (PR) bleeding – the major risk factor for these is constipation or straining at stool, as well as being common in pregnancy. They do not increase the risk of colorectal cancer. Hamartoma Hamartomas are benign focal growths within an organ comprised of cells/tissue that normal ly arise from that organ but have developed into an abnormally structured growth. They resemble neoplasms but are do not have malignant potential. There are, however, syndromes in which multiple hamartomas are present that can result in increased risk of malignancy. Cowden’s syndrome is characterized by multiple hamartomas throughout the gastrointestinal (GI) tract, skin, thyroid and other organs, and while the hamartomas themselves are benign, the patient has an increased risk of malignancy due to mutations in the PTEN tumour suppressor gene. Angiodysplasia Angiodysplasia are arteriovenous malformations within the gastrointestinal tract which may be single or multiple. They are usually asymptomatic but can present with acute episodes of painless bleeding or malena (depending on their position within the GI tract). Chronic bleeding may lead to anaemia. Solitary polyp Solitary juvenile polyps are benign hamartomatous polyps, most commonly found in the rectum and occurring before the age of 20 (although they can occur at any age). The term juvenile describes the polyp, not the age of the patient. They may present with rectal bleeding, but do not predispose to cancer. This is in contrast to juvenile polyposis syndrome where multiple mostly hamartomatous polyps are found either within the rectum and colon, or throughout the GI tract – with an increased risk of adenocarcinoma.

Answer 222

Explanation The incidence is declining world-wide This statement is correct, the incidence of gastric cancer is declining world-wide. The incidence of gastric cancer in the UK is between 6500–7000 cases a year and is also declining, the highest risk age group being 85–90-year-olds. It is decreased in patients with chronic atrophic gastritis Chronic atrophic gastritis is a condition where chronic inflammation of the gastric mucosa leads to a gastric glandular atrophy and loss of parietal cells (therefore a decrease in production of peptic acid and intrinsic factor), replaced by intestinal metaplasia and fibrous tissue deposition. This condition can present with chronic stomach pain, nausea, vomiting and weight loss, and with a megaloblastic anaemia due to lack of vitamin B 12 absorption. The commonest predisposing conditions are H. pylori infection and autoimmune gastritis. Chronic atrophic gastritis and resultant intestinal metaplasia both lead to increased gastric cancer risk. It is higher among women The male to female ratio is approximately 2:1. It is highest in India The highest rates of gastric cancer occur in Japan, Mongolia and Korea, while most cases world - wide are in developing countries. It is reduced in patients with blood group A The incidence of stomach cancer has been shown to be 20% higher in those with blood group A compared to those with blood group O.

Answer 223

Explanation Intussusception Intussusception is a condition in which a portion of the bowel telescopes within an adjacent segment of bowel. Most commonly this is the ileum entering the caecum. Sometimes an anatomical lead point is identified as causing the intussusception – this may be a Meckel’s diverticulum, polyp or a hyper plastic Peyer’s patch (ie from a rece nt viral infection). It classically presents with the triad of rectal bleeding, vomiting and abdominal pain. The rectal bleeding is often described as like red currant jelly. An abdominal mass (the intussuscepted segment) may be palpable. Ultrasound is the investigation of choice initially, and treatment is with either barium or water - soluble enema (which will usually both visualise and reduce the intussusception). If this fails surgical reduction may be required. Anal fissure Anal fissures present with pain and fresh per rectal (PR) bleeding on passing stool, often noticed most on wiping rather than in the stool itself. The main risk factor is constipation. The pain is felt at the site of the fissure rather than intra-abdominally (although this may be difficult to determine in a 6-month-old infant. This condition would not explain the vomiting, ‘redcurrant jelly’ or the abdominal mass. Hamartomatous polyp Hamartomas are benign focal growths within an organ comprised of cells/tissue that normally arise from that organ but have developed into an abnormally structured growth. They resemble neoplasms but do not have malignant potential. Within the gastrointestinal (GI) tract they may present with GI bleeding, but the description of ‘red currant jelly stool’ is classical for intussusception. Inflammatory bowel disease Inflammatory bowel disease (IBD) could explain this patient’s symptoms (Crohn’s disease, for example, can present with an inflammatory right iliac fossa mass), however, it would be unusual to present in such a young child and usually presents between the ages of 15 –25. It is by no means the most likely diagnosis offered here. Rectal ulceration This option is a rare, benign condition in childhood that usually presents with per rectal (PR) bleeding and mucous, lower abdominal and perineal pain, and constipation. It would not explain the patient’s abdominal mass or vomiting. The most likely diagnosis in this scenario is intussusception. Other causes of rectal bleeding in children not considered above inclu de Meckel’s diverticulum, vascular malformations, and Henoch–Schönlein purpura.

Answer 224

Explanation When following Goodsall's rule, in the case of an anterior fistula, the internal opening follows a direct path Goodsall’s rule states that an external opening lying anterior to Goodsall’s line (the transverse anal line) is usually associated with a straight tr act, whereas an external opening lying posterior to it may follow a curving tract. They always start from an abscess A fistula is an abnormal communication between two epithelialized surfaces. Up to 80% of anal fistulas are due to an anorectal abscesses. Other causes include post-surgical complications, trauma, penetrating injury, tuberculosis (TB) infection or Crohn’s disease. They are always associated with Crohn's disease They can be caused by Crohn’s disease. Most, however, start from an abscess, while others develop insidiously or from causes such as haemorrhoidectomy, trauma, penetrating injury, TB infection or tumours They are initially managed with antibiotics Antibiotics are used in cases complicated by cellulitis or sepsis, or if the patient is immunocompromised. The treatment of the fistula itself in simple cases is with fistulotomy, while in other cases other techniques may be required/indicated such as the Ligation of the Intersphincteric Fistula Tract (LIFT) procedure or Seton sutures. In the case of complex fistulae the investigation of choice is a contrast CT Complex fistulae are best imaged by a magnetic resonance imaging (MRI) scan.

Answer 225

Explanation Recurrent abscess A fistula is an abnormal communication between two epithelialized surfaces. Up to 80% of anal fistulas are due to an anorectal abscesses. Other causes include post -surgical complications, trauma, penetrating injury, tuberculosis (TB) infection or Crohn’s disease. Carcinoma This option is a cause, but not the most common. Ulcerative colitis Fistula are common in Crohn’s disease, however, because inflammation in ulcerative colitis is confined to the mucosa and submucosa (rather than being transmural as in Crohn’s) fistula are not classically seen in ulcerative colitis. Trauma This option is a cause, but not the most common. Tuberculosis This option is a cause, but not the most common.

Answer 226

Explanation Female sex Men are affected three to four times more often than women. Age of patient Pilonidal sinus is a condition predominantly affecting young adults between the ages of 20 and 40 years. Hirsutism Risk factors include hirsutism, obesity, prolonged sitting as part of normal daily routine, family history, male sex, and deep natal cleft. Recurrence of condition following surgery If an abscess forms then treatment is incision and drainage, while chronic discharging sinuses or recurrent abscesses may require removal of the tract or laying it open and allowing it to heal by secondary intention. Reported recurrence rates vary but may be up to 50%. Obesity Patients may frequently be described as hairy and may also be obese. A pilonidal sinus is usually found in the midline in the natal cleft. The cause is unclear although a loose hair piercing the skin is thought to be attributable. These may be asymptomatic, or present acutely with abscess formation, or chronically with ongoing discharge.

Answer 227

Explanation Ophthalmoscopy or DNA screening DNA screening is 95% predictive. In addition, it is important to note that many patients with FAP are found to have bilateral lesions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) on ophthalmoscopy. DNA screening - gene present on short arm of chromosome 15 The gene is present on the short arm of chromosome 5. Male children only of known FAP patients need will be screened FAP, due to mutation of t he APC gene, is an autosomal-dominant condition that affects men and women equally. Sigmoidoscopy and biopsy after adenomas become symptomatic Diagnosis in new patients with new mutations and no family history is usually by sigmoidoscopy and biopsy after t he adenomas become symptomatic. If 100 or more adenomas are present, FAP is presumed. Such children are most likely to present with carcinoma of the colon or rectum The risk of malignancy in FAP is almost 100%. However, this risk increases with age, and children rarely present with carcinoma. Polyps may be visible from age 7, but the risk of cancer is 7% at 21, rising to almost 100% by age 50.

Answer 228

Explanation Pseudopolyps can be inflammatory An inflammatory polyp is an island of inflamed mucosa surrounded by ulcerated tissue, a classic example of this is in ulcerative colitis – called pseudopolyps. Hamartomatous polyps are made up of smooth muscle cells Hamartomas are benign focal growths within an organ comp rised of cells/tissue that normally arise from that organ but have developed into an abnormally structured growth – they resemble neoplasms but do not have malignant potential. Over 25% of the population over 45 years of age may have asymptomatic adenomas Approximately 25% of men and 15% of women over the age of 50 years may have an adenoma identified at colonoscopy. They usually bleed on contact Benign adenomas do not usually bleed on contact, bleeding is more common if the polyp is malignant. Their malignant potential is indirectly related to the size of the lesion The guidelines from NICE recommend ongoing screening for all patients with polyps found on colonoscopy at 5-yearly intervals. However, if any of the polyps found are ³10mm in diameter then this screening should be at 3- or 1-yearly intervals, depending on the number of polyps.

Answer 229

Explanation Reassurance and advice on eating an increased fibre diet First-degree haemorrhoids may respond to increasing fibre in the diet or to bulking agents. Reassurance that symptoms are due only to haemorrhoids is important. Bedrest and analgesia Thrombosed strangulated haemorrhoids may be treated conservatively with analgesia, bedrest, elevated legs and an icepack or by surgery. Elevated legs and an ice pack Thrombosed strangulated haemorrhoids may be treated conservatively with analgesia, bedrest, elevated legs and an icepack or by surgery. No treatment should be given Asymptomatic haemorrhoids should not be treated but reassurance and advice regarding a high - fibre diet is important. Surgery Thrombosed strangulated haemorrhoids may be treated conservatively with analgesia, bedrest, elevated legs or an icepack. Symptomatic first - and second-degree haemorrhoids that have persisted despite medical intervention can be treated with rubber band ligation or injection sclerotherapy, whereas third-degree haemorrhoids are ideally managed by formal haemorrhoidectomy. Haemorrhoids are swollen vascular cushions that affect approximately 40% of patients at some point. The most common presenting symptoms are noticeable prolapse and fresh rectal bleeding, they may also cause pruritus or pain. Risk factors include constipation and straining at stool, increasing age, or increased intra-abdominal pressure (eg pregnancy, pelvic masses). Haemorrhoids can be internal or external, external arising below the dentate line. If internal they can then be described as first - through to fourth-degree: 1st – Haemorrhoids within lumen of the anal canal, no prolapse. 2nd – Haemorrhoids prolapse on straining but spontaneously reduce when straining is stopped. 3rd – Haemorrhoids prolapse but are fully reducible with manual pressure. 4th – Haemorrhoids are irreducibly prolapsed.

Answer 230

Explanation Sigmoid colon Almost 50% of cases affect the sigmoid alone while a further nearly 25% of cases affect the sigmoid and descending colon. In total the sigmoid colon is involved in over 80% of cases. Ascending colon Right-sided diverticula are present in fewer than 20% of cases in the Western population. However, in the Asian population, right -sided diverticula are more common, although this is changing with the adoption of a Western diet. Caecum Right-sided diverticula are present in fewer than 20% of cases in the Western population. However, in the Asian population, right -sided diverticula are more common, although this is changing with the adoption of a Western diet. Rectum Rectal diverticula are extremely rare, presenting in less than 1% of cases Transverse colon The most common site for diverticula is the sigmoid colon. Diverticulosis descr ibes the presence of pouches of protruding mucosa through the colonic wall. They primarily occur in the large bowel where the longitudinal outer layer of muscle is arranged as distinct bands called ‘taenia coli’ that give rise to sites of relative weakness in-between the bands. Presence of diverticula increases with age – it affects approximately 50% by 50 years of age and 70% by 80 years of age. It is most common in the descending and sigmoid colon in the Western population, but can occur throughout the co lon. The most important modifiable risk factor appears to be lack of dietary fibre and resultant constipation. Diverticular disease is the term used to refer to symptomatic diverticulosis – the most common symptoms being altered bowel habit (often alternat ing between constipation and diarrhoea) and lower abdominal pain. It is not a premalignant condition but can co -exist with colorectal cancers. Diverticulitis is an acute inflammatory exacerbation of pre-existing diverticulosis. This usually presents with left iliac fossa pain, fever and can also present with per rectal (PR) bleeding.

Answer 231

Explanation Arterial pa (O2 ) of 7 kPa This is correct – arterial partial pressure of oxygen of < 8 (< 60 mmHg) is one of Ranson’s criteria. Ranson’s criteria are used to predict severe pancreatitis and a prognosis of approximate mortality. It was initially described for alcoholic (ie non-gallstone) pancreatitis. Several factors are assessed at presentation and again at 48 h to give the full score. 1 point is given for each criterion present, and this allows the following prognosis:  0–2 points = 1% mortality from this episode  3–4 points = 15% mortality  5–6 points = 40% mortality  7 or more points = 100% mortality Amylase 2600 IU/l Amylase (normal value < 200 U/l) is a useful diagno stic investigation for pancreatitis. It is not, however, prognostically useful. Corrected serum calcium of 2.6 mmol/l Corrected serum calcium of < 2.0 mmol/l scores a point in Ranson’s criteria and would therefore indicate poor prognosis. Leukocyte count of 5 × 10 9 /l A white-cell count greater than 16 × 10 9 /l scores a point in Ranson’s criteria and would therefore indicate poor prognosis. Rise in packed-cell volume by more than 10% Packed-cell volume indicates the volume of red cells circulating as a perce ntage of total blood volume. It is raised most commonly in dehydration or in excess production of red cells – it is not part of Ranson’s criteria. A fall in haematocrit at 48 h by > 10% from admission does score, however.

Answer 232

Explanation Sporadic factor Around 65% of colorectal cancers are thought to be sporadic – ie the genetic mutations present within these cancers are not inherited. Important risk factors in developing sporadic colorectal cancer include age, diet rich in red meat and lo w in fibre, smoking and obesity. Familial adenomatous polyposis (FAP) Less than 1% of colorectal cancer is attributable to FAP. Hereditary nonpolyposis colorectal cancer (HNPCC) This accounts for approximately 2–4% of colorectal cancers. Other familial colon cancer syndrome (excluding FAP/HNPCC) Inheritance is a factor in up to one-third of colorectal cancer cases; however, only 5% of colorectal cancers arise in the setting of an inherited colorectal cancer syndrome – this number includes FAP and HNPCC, which are the most common. Pre-existing inflammatory bowel disease (IBD) IBD-related colorectal cancer accounts for < 2% of all colorectal cancers.

Answer 233

Explanation They are more common in urban areas than rural areas Both Crohn’s disease and ulcerative colitis are more common in those living in urba n areas compared with rural areas. The following table summarises key aspects of Crohn’s disease and ulcerative colitis. Crohn’s disease Ulcerative colitis Prevalence 145 per 100 000 240 per 100 000 Segments affected Any part of the alimentary tract from mouth to anus, most commonly the terminal ileum. Commonly spares the rectum Affects the rectum, extending contiguously proximally a variable amount but limited to the colon Pattern of disease Skip lesions Continuous Macroscopic Cobblestones, aphthous and linear ulcers, ‘rose-thorn’ ulcers, abscesses, luminal Pseudopolyps, very friable mucosa, featureless colon, findings narrowing or stricturing decreased haustrae, shortened colon, toxic megacolon Microscopic findings Transmural inflammation, granulomas Submucosal or mucosal inflammation, crypt abscesses Common symptoms Abdominal pain, diarrhoea, weight loss, mouth ulcers, perianal disease Bloody diarrhoea, weight loss, abdominal pain Extraintestinal features Perianal disease (fissures, fist ulae, tags, abscesses), mouth ulcers, oral aphthous ulcers, erythema nodosum, arthritis and spondyloarthropathies, uveitis, episcleritis Primary sclerosing cholangitis, arthritis and spondyloarthropathies, uveitis, episcleritis Any part of alimentary cana l affected from mouth to anus Crohn’s disease can affect any part of the alimentary canal, with mouth ulcers and perianal disease common features. It classically produces skip lesions whereby different parts of the bowel are affected in a discontinuous manner. Ulcerative colitis affects the rectum and a variable but continuous amount of proximal large bowel. Backwash ileitis can occur, causing inflammation of the terminal ileum but otherwise the small bowel is not affected. Small, shallow ulcers Small, shallow ulcers are typical of ulcerative colitis; those seen in Crohn’s disease tend to be very deep. In 30% of cases, only the ileum is affected In Crohn’s disease, only the ileum is affected in 30% of cases. Ulcerative colitis will not affect the ileum, except in some cases in which backwash ileitis can occur (less than 10%). 60% of cases are confined to rectum and sigmoid In ulcerative colitis, 60% of cases are confined to the rectum and sigmoid colon. Crohn’s disease classically causes skip lesions thro ughout the entire alimentary tract from mouth to anus, but the rectum is commonly spared.

Answer 234

Any part of the alimentary tract from mouth to anus, most commonly the terminal ileum. Commonly spares the rectum Skip lesions Ulcerative colitis Prevalence Segments affected Pattern of disease 240 per 100 000 Affects the rectum, extending contiguously proximally a variable amount but limited to the colon Continuous Macroscopic Cobblestones, aphthous and linear ulcers, Pseudopolyps, very friable findings ‘rose-thorn’ ulcers, abscesses, luminal narrowing or stricturing mucosa, featureless colon, decreased haustrae, shortened colon, toxic megacolon Microscopic findings Transmural inflammation, granulomas Submucosal or mucosal inflammation, crypt abscesses Common symptoms Abdominal pain, diarrhoea, weight loss, mouth ulcers, perianal disease Bloody diarrhoea, weight loss, abdominal pain Extraintestinal features Perianal disease (fissures, fistulae, tags, abscesses), mouth ulcers, oral aphthous ulcers, erythema nodosum, arthritis and spondyloarthropathies, uveitis, episcleritis Primary sclerosing cholangitis, arthritis and spondyloarthropathies, uveitis, episcleritis Affects rectum and spreads proximally Crohn’s disease can affect any part of the alimentary canal, with mouth ulcers and perianal disease common features. It classically produces skip lesions whereby different parts of the bowel are affected in a discontinuous manner. Ulcerative colitis usually affects the rectum and a variable but continuous amount of proximal large bowel, backwash ileitis can occur causing inflammation of the terminal ileum, but otherwise the small bowel is not affected. Featureless ‘lead pipe’ colon A featureless ‘lead pipe’ colon can occur in chronic ulcerative colitis in affected segments due to the inflammation and oedema resulting in loss of haustrae. Thumbprinting Thumbprinting is a relatively non-specific sign suggesting colonic oedema, which ma y be present in ulcerative colitis. It is, however, a feature of plain radiographs, not of barium enema. Small ulcers Ulcers in Crohn’s disease are typically deep because inflammation is transmural and the mucosa has a cobblestoned appearance.

Answer 235

Explanation It has a positive family history with those with a first degree relative affected having a 15% lifetime risk of developing the disease Those with a first degree relative have up to a 15% lifetime chance of developing ulcerative colitis. It has a prevalence of approximately six cases per 100 000 of the population The prevalence in the UK is around 240 per 100 000 population. It is always confined to the rectum Ulcerative colitis always affects the rectum w ith a variable involvement proximally in a continuous manner. It is confined to the large bowel with the exception of occasional cases of backwash ileitis, in which the terminal ileum is inflamed. Otherwise, it does not affect the small bowel. It is invest igated by ultrasound as the investigation of choice Colonoscopy with biopsy is the gold standard investigation for diagnosis and sub-classification of inflammatory bowel disease. It is not a pre-malignant condition There is malignant potential in ulcerative colitis – after ten years, the risk is around 2%, then 8% at 20 years and 18% at 30 years. Those with ulcerative colitis for ten years or longer are offered surveillance at between 1–5-yearly intervals depending on whether they are deemed low, intermediate or high-risk of developing colorectal cancer.

Answer 236

Explanation Alcoholic liver disease Jaundice with an elevation of both AST and alkaline phosphatase suggests mixed hepatocellular damage and cholestatic liver disease, typical of acute alcoholic hepatitis on a background of chronic liver disease (and is not excluded by the lack of physical signs). The high g - glutamyltransferase lends support to this as it is typically elevated in alcoholism (although it may be increased in liver disease of any cause). A mild macrocytosis is typical of chronic excessive alcohol intake and is not a feature of the other conditions. AST and alanine a minotransferase (ALT) are enzymes released from hepatocytes when they are damaged; therefore, when hepatocellular damage predominates, these enzymes will be raised. ALP is typically raised where cholestasis is present. Autoimmune chronic hepatitis Autoimmune chronic hepatitis typically causes a hepatocellular damage. You would therefore expect AST to be raised with much lesser change in ALP. Non-metastatic carcinoma of the head of the pancreas In patients presenting with painless jaundice, a diagnosis of pa ncreatic cancer causing an obstructive jaundice should be considered. The mixed picture of cholestasis and hepatocellular damage, however, does not fit with pancreatic cancer which normally causes a cholestasis – the ALP would be expected to be elevated with much lesser AST elevation. Cholecystitis Chronic cholecystitis can cause jaundice but it would be unusual for there to be no history of acute episodes. Additionally, the cause of jaundice in these patients is normally due to obstruction, either due to a common biliary duct stone or because of local inflammation putting pressure on the biliary tree – an obstructive/cholestatic pattern would be more suggested by a high ALP and normal or only mildly elevated AST. Hepatitis A infection In hepatitis A, a hepatocellular picture develops so AST is typically higher than alkaline phosphatase. This infection causes hepatitis and results directly in hepatocellular damage.

Answer 237

Explanation Benign prostatic hyperplasia (BPH) affects 50% of men over 50 The proportion of men affected increases with increasing age, and the prevalence of lower urinary tract symptoms also increases with age. However, many of the 50% will have only mild or moderate symptoms, which are acceptable to them without treatment. The severity of symptoms is related to the size of the prostate gland The severity of symptoms is not related to the size o f the gland but to the encroachment on the prostatic urethra and the resulting obstruction to urinary flow. Finasteride, a 5-alpha-reductase inhibitor, will decrease the size of the prostate gland within a week and therefore allow a trial without a catheter Finasteride is an alpha-reductase inhibitor, which blocks the conversion of testosterone to dihydrotestosterone and reduces the size of the hyperplastic glands. A 6 -month trial of treatment is required and symptoms may be reduced or delayed or even avoid surgery. Alpha-adrenergic blockers can be used to relax bladder neck muscle fibres and fibres in the prostate gland, and take effect within a week. Benign prostatic hyperplasia will not increase prostate-specific antigen (PSA) Normal levels increase with age. Benign prostatic hyperplasia (BPH) can cause a small rise in PSA, but the higher the rise in PSA the more specific it is for prostate cancer: > 4.1 ng/ml = 9.1%, > 10 = 55.5%. The aim of transurethral prostatectomy is to core out the whole prostate The aim of transurethral resection of the prostate (TURP) is to debulk the prostate gland surrounding the urethra and leave the normal peripheral tissue.

Answer 238

Explanation If no mutation can be identified then family members should be screened for the condition using colonoscopy or flexible sigmoidoscopy from 13–15 years of age The British Society of Gastroenterology guidelines suggest that relatives of the patient who have a 50% risk of FAP should be offered yearly large bowel surveillance from the age of 13 –15 until the age of 30. From then, 3–5-yearly screening until they are 60 is advised. As FAP is an autosomal-dominant condition, the children of the patient will have a 50% risk of the condition, so should be offered screening as above. A specific collection of signs/symptoms in FAP is known as Gardner syndrome. Desmoid tumours occurring as part of FAP are benign and do not cause any problems Desmoid tumours, which are solid tumours of the connective tissues, particularly within the abdomen, occur in up to 15% of people with FAP. Although they are not malignant, they can cause major problems by aggressively invading surrounding tissues. Desmoid tumours account for up to 11% of deaths in those with FAP. Colonic cancer is the only malignancy associated with FAP Individuals affected with FAP risk developing a duodenal malignancy, other small bowel cancers, thyroid cancer, pancreatic cancer, adrenal cancer, and hepatoblastoma. FAP affects 1 in 1000 people FAP affects 1 in 10 000 people. Men and women are equally affected. The FAP adenomatous polyposis coli (APC) gene shows an autosomal-recessive form of inheritance FAP is autosomal-dominant. About 20–30% of cases seem to arise from new mutations.

Answer 239

narrowing or stricturing decreased haustrae, shortened colon, toxic megacolon Microscopic findings Transmural inflammation, granulomas Submucosal or mucosal inflammation, crypt abscesses Common symptoms Abdominal pain, diarrhoea, weight loss, mouth ulcers, perianal disease Bloody diarrhoea, weight loss, abdominal pain Extraintestinal features Perianal disease (fissures, fist ulae, tags, abscesses), mouth ulcers, oral aphthous ulcers, erythema nodosum, arthritis and spondyloarthropathies, uveitis, episcleritis Primary sclerosing cholangitis, arthritis and spondyloarthropathies, uveitis, episcleritis Both Crohn’s disease and ulcerative colitis start then spread from the rectal mucosa Ulcerative colitis always involves the rectum with disease then spreading proximally throughout the colon. There can be backwash ileitis where there is some involvement of the terminal ileum, but ulcerative colitis is really a colonic disease. Ulcerative colitis remains confined to the rectum in approximately 25% of cases. In the remainder of cases, it spreads proximally and contiguously. Pancolitis occurs in 10% of patients. Crohn’s disease, convers ely, consists of segmental involvement by a non-specific granulomatous inflammatory process. The most important pathological feature is involvement of all layers of the bowel, not just the mucosa, and the submucosa as is characteristic of ulcerative colitis. Crohn’s disease has a clear demarcation between involved and uninvolved mucosa, whereas ulcerative colitis shows skip lesions with normal mucosa in-between Crohn’s disease is discontinuous, with skip areas interspersed between one or more involved areas. Late in the disease, the mucosa develops a cobblestone appearance, which results from deep longitudinal ulcerations interlaced with intervening normal mucosa. The three major patterns of involvement in Crohn’s disease are:  disease in the ileum and caecum, occurring in 40% of patients  disease confined to the small intestine, occurring in 30% of patients  disease confined to the colon, occurring in 25% of patients. Weight loss is more commonly seen in ulcerative colitis than in Crohn’s disease Weight loss is more commonly seen with Crohn’s disease due to the loss of absorptive capacity in the small bowel. Ulcerative colitis is more likely to present with bloody diarrhoea and symptoms suggestive of an inflamed rectum, such as tenesmus and urgency. Fistulae are often seen in both diseases Fistulae are not usually seen in ulcerative colitis because there is only mucosal and submucosal involvement in the large bowel. Crohn’s disease, however, has full-thickness involvement of the bowel wall and can therefore form a fistula with nearby structures, eg recto -vaginal, recto- vesical.

Answer 240

Explanation On abdominal X-ray a transverse colonic diameter of 8cm is significant The transverse colon is often used as the point of reference for dilatation, its normal diameter = 5.5–6.5 cm. Loss of colonic haustra is also seen, and possible thumbprinting – a coarse, irregular, mucosal pattern of the large bowel. Toxic megacolon is due to large bowel obstruction causing dilat ation of the colon The hallmarks of toxic megacolon, a potentially lethal condition, are non-obstructive colonic dilatation larger than 6 cm and signs of systemic toxicity. Toxic megacolon does not occur in Crohn’s disease Toxic megacolon may complicate any number of colitides, including inflammatory bowel disease – which is the most common aetiology (around 50%). Other causes include ischaemic, infectious (Clostridium difficile), radiation, and pseudomembranous colitis. It is more common in ulcerative colitis but can also occur in Crohn’s disease. Mortality rates in Toxic megacolon of any aetiology are 40% Mortality rates have been falling due to better care and earlier surgical involvement, and are now quoted as being 5–20%. Once perforation has occurred mortality rates are thought to increase five-fold. First line treatment is surgical resection Initial management is medical. During the initial resuscitation, fluid and electrolyte replacement, and transfusion should be aggressive. Broad-spectrum intravenous antibiotics should be initiated. All medications that may affect colonic motility must be stopped. These include narcotics, antidiarrhoeals, and anticholinergic agents. The patient should be put on bowel rest, and a nasogastric tube placed to assist with gastrointestinal (GI) decompression. If the patient has underlying inflammatory bowel disease then this should be treated too. Should medical management fail then surgical resection will be required.

Answer 241

Explanation If infected pancreatic necrosis develops the mortality rate is approximately 25% This is correct, this rate compares with that of mild acute pancreatitis, which has a mortality of around 1%, and sterile pancreatic necrosis at 10%. About 20 –30% of patients with acute pancreatitis develop complications of necrosis or organ failure. Due to the wide spectrum of the disease, several systems have been developed in an attempt to provide reliable prognostic classification for patients. The most frequently used of these is the modified Glasgow score. Modified Glasgow score criteria:  pa (O2 ) < 7.9 kPa  age > 55 years  neutrophils (white blood cell (WBC) > 15)  calcium < 2 mmol/l  urea > 16 mmol/l  LDH > 600 IU/l  albumin < 32 g/L (serum)  blood glucose > 10 mmol/l If three or more of these criteria are present in the first 48 h of admission then severe pancreatitis is likely. Various scores can also be used to estimate mortality:  score 0 to 2: 2% mortality  score 3 to 4: 15% mortality  score 5–6: 40% mortality  score 7 to 8: 100% mortality. Feeding via the total parentral route is preferred as it prevents over stimulation of the pancreas Opinion has recently changed regarding feeding in pancreatitis. It is now best practice to feed by the enteral route via a feeding tube placed past the pancreatic duct into the 3rd part of the duodenum. For milder cases, patients can have oral intake as this is tolerated. Serum amylase is a reliable marker of severity and progression of pancreatitis Although amylase and lipase levels are useful in the diagnosis of pancreatitis they have no role i n assessing severity – for example, neither is used in the Ranson scoring system used to prognosticate acute pancreatitis. Lipase rises in 4–6 h and normalises in 7–14 days. Amylase may be normal in 10% of cases. The APACHE II scale is the most commonly used prognostic scale in acute pancreatitis The APACHE II is a scoring system designed to assess disease severity patients admitted to the ITU. It has been well studied in acute pancreatitis, but by design is an admission score designed to assess disease severity in all adult patients admitted to general ITU. It uses the patients age, and various physiology and biochemical/laboratory values within the first 24 h of admission. A higher score corresponds to a higher severity of disease and a higher risk of deat h from this admission. The most frequently used prognostic classification for patients with acute pancreatitis is the modified Glasgow score. The BALTHAZAR scoring system assesses severity of pancreatis using serial ultrasound scans The BALTHAZAR score is a computed tomography (CT) scan-based scoring system that is used to grade the severity of pancreatitis.

Answer 242

Explanation It is post-hepatic jaundice This is correct – neoplasms classically within the head of the pancreas can compress or invade and obstruct the common bile duct. This leads to an obstructive or cholestatic jaundice. Bilirubin is principally derived from the degradation of haemoglobin within the spleen and is carried to the liver bound to albumin, as in its unconjugated form it is not water soluble. Within the liver, bilirubin is conjugated by glucuronyltransferase, making it water soluble, and is secreted into the duodenum. At the distal ileum the bilirubin is either converted to urobilinogen and excreted in the faeces as stercobilinogen, or is re-absorbed and renally excreted. Jaundice becomes clinically apparent at serum levels >35–40 µmol/l. Jaundice may be classified as pre-hepatic, hepatic, or post -hepatic, depending on the site of the obstruction or metabolic abnormality.  Pre-hepatic (haemolytic) jaundice: caused by disorders resulting in increased destruction of red cells, eg autoimmune haemolytic anaemia or sickle cell disease which overwhelms the livers ability to process the excess bilirubin. The excess bilirubin is unconjugated so no bilirubin is detected in the urine. Hepatic (parenchymal) jaundice: caused by any condition affecting hepatocyte function, eg acute hepatitis infection, alcoholic hepatitis, drug-induced hepatitis, or cirrhosis of any cause.  Post-hepatic (cholestatic) jaundice: caused by physical obstruction of the biliary system eg carcinoma of the head of pancreas or gallstones. Typically there is dark urine (the bilirubin is water soluble, so is excreted in the urine) and pale stools (due to steatorrhoea from lack normal biliary function in aiding fat absorption). It is due to excess bile production Jaundice is a result of excess bilirubin, while bilirubin is excreted in the bile excess bile production would not be expected to result in jaundice. It is due to haemolytic anaemia Haemolytic anaemia is an example of pre-hepatic jaundice – it is not the correct answer in this instance. It is part of a paraneoplastic syndrome Paraneoplastic syndromes are effects of malignancy not caused by the local effect of the cancer itself – they are frequently hormo nal or immunological. Examples include Cushing syndrome in small-cell lung cancer caused by ectopic adrenocorticotropic hormone (ACTH) production, or Lambert–Eaton myasthenia syndrome caused by antibodies produced against small-cell lung cancer that are active against pre-synaptic voltage gated calcium channels. Paraneoplastic syndromes associated with pancreatic cancer include Cushing syndrome, carcinoid syndrome and dermatomyositis. It is secondary to tumour lysis syndrome Tumour lysis syndrome is a potential treatment complication of most commonly, haematological cancers. Rapid lysis of leukaemia or lymphoma cells results in metabolic abnormalities including hyperkalaemia, hyperphosphataemia, hypocalcaemia, lactic acidosis and hyperuricaemia. It is potentially life-threatening – however, it does not usually result in jaundice.

Answer 243

Explanation Primary biliary cirrhosis Primary biliary cirrhosis frequently presents first with progressive and insidious onset of pruritus and general malaise/lethargy, jaundice occurring later in the disease process. It is more common in women than men (ratio 9:1), classically presenting between 40 –60 years of age. It is an autoimmune condition associated with antimitochondrial antibodies, and the presence of excessive antibodies is suggested by the slight ele vation in total protein with low–normal albumin (this suggests a high globulin concentration). The disease process results in progressive destruction of the intrahepatic bile ducts, and therefore an obstructive/cholestatic jaundice supported by the raised alkaline phosphatase (ALP), but relatively normal aspartate transaminase (AST). Alcoholic cirrhosis Alcoholic cirrhosis is a common cause of the above picture but is unlikely (although not excluded) by the absence of history of alcohol excess, and the only slightly elevated g- glutamyltransferase (which is sensitive, although non-specific, for alcohol excess). Carcinoma of the head of the pancreas Carcinoma of the head of the pancreas frequently presents in this manner (although weight loss is often present also), but the slight elevation in total protein with low –normal albumin suggests a high globulin concentration, which suggests autoimmune liver disease. Cholangiocarcinoma Cholangiocarcinoma is a rare tumour, although could present like this. As with carc inoma of the head of the pancreas, weight loss is often present also, and the slight elevation in total protein with low–normal albumin suggests a high globulin concentration, which suggests autoimmune liver disease. Primary sclerosing cholangitis Primary sclerosing cholangitis is a possibility but is commoner in men than women (3:1), and in 75% of cases are associated with inflammatory bowel disease. In this case primary biliary cirrhosis is more likely.

Answer 244

Gilbert syndrome is an inherited, autosomal-recessive condition resulting in abnormal liver metabolism of bilirubin. It is relatively common affecting around 5% of the population. The correct laboratory test to confirm a diagnosis of Gilbert syndrome is 1) Absence of bilirubin in the urine. In Gilbert syndrome, there is an increase in unconjugated bilirubin, which is water-insoluble and does not appear in the urine. Diagnosis is typically supported by elevated serum unconjugated bilirubin with normal liver function tests and no evidence of hemolysis Gilbert syndrome is normally asymptomatic, but mild jaundice may develop whe n there is physiological stress (eg infection or fasting). In Gilbert syndrome, the excess bilirubin is unconjugated, and does not appear in the urine. You would also not expect to find bilirubin the urine in other causes of pre-hepatic jaundice, such as haemolytic disease. Decreased serum haptoglobin concentration Decreased serum haptoglobin concentration is a sign of haemolytic anaemia. Haptoglobin will bind free haemoglobin released by lysed red cells and this complex is then removed by the spleen. Elevated serum aspartate aminotransferase (transaminase, AST) activity Elevated AST is a non-specific sign of hepatocellular damage – the excess activity being detected in the blood a result of the release of these enzymes from their normal intracellular site within hepatocytes. This would be raised, for example, in alcoholic hepatitis, viral hepatitis, or drug-induced liver damage. Haemolysis may also cause a slight increase in serum aminotransferase (transaminase) activity as red blood cells also have a small amount of AST within them. AST is also found in skeletal muscle among other cell types. Increased reticulocyte count This is a sign of excess haemolysis – the rapid destruction of red blood cells resulting in rapid production of red blood cells and therefore an increased number of reticulates in the peripheral blood count. Increased urinary urobilinogen excretion However, in haemolytic jaundice, urinary urobilinogen is increased (increased production of bilirubin, and hence of urobilinogen), the reticulocyte count may be elevated and serum haptoglobin concentration decreased. Bilirubin is principally derived from the degradation of haemoglobin within the spleen and is carried to the liver bound to albumin, as in its unconjugated form it is not water soluble. Within the liver bilirubin is conjugated by glucuronyltransferase, making it water soluble, and is secreted into the duodenum. At the distal ileum the bilirubin is either converted to urobilinogen and excreted in the faeces as stercobilinogen, or is re-absorbed and renally excreted. Jaundice becomes clinically apparent at serum levels >35–40 µmol/l. Jaundice may be classified as pre-hepatic, hepatic, or post -hepatic, depending on the site of the obstruction or metabolic abnormality.  Pre-hepatic (haemolytic) jaundice: caused by disorders resulting in increased destruction of red cells eg autoimmune haemolytic anaemia or sickle cell disease which overwhelms the livers ability to process the excess bilirubin. The excess bilirubin is unconjugated so no bilirub in is detected in the urine.  Hepatic (parenchymal) jaundice: caused by any condition affecting hepatocyte function eg acute hepatitis infection, alcoholic hepatitis, drug-induced hepatitis, or cirrhosis of any cause.  Post-hepatic (cholestatic) jaundice: caused by physical obstruction of the biliary system eg carcinoma of the head of pancreas or gallstones. Typically there is dark urine (the bilirubin is water soluble, so is excreted in the urine) and pale stools (due to steatorrhoea from lack normal biliary function in aiding fat absorption).

Answer 245

Explanation Pseudo-obstruction Pseudo-obstruction is an example of non-mechanical bowel obstruction. It can be acute or chronic. Acute is also known as Ogilvie syndrome. In 80% of cases, colonic pseudo -obstruction is associated with other clinical conditions. The most common are cardio -respiratory illness, post-trauma or pelvic surgery. It usually presents as this clinical vignette with abdominal distension in the context of another acute condition, intermittent constipation and nausea or vomiting are frequent symptoms, colicky abdominal pain may be present. Imaging will reveal dilated bowel loops. Treatment should be based on correcting the associated cause such as the respiratory illness or correcting electrolyte imbalances – usually potassium, magnesium or phosphate. This may resolve the ‘obstruction’. Otherwise consider endoscopic decompression. Neostigmine has also been used in some chronic cases. Colorectal cancer Colorectal cancer, particularly left -sided lesions, can cause and therefore present with obstruction, which would give abdominal distension and dilated bowel loops. However, mechanical obstruction is frequently painful. Usually colorectal cancer pres ents insidiously with a change in bowel habit or PR bleeding, or with an otherwise unexplained microcytic anaemia. Constipation Constipation is a frequent complication for patients in hospital, both because of medication used (for example opiates) and because many patients are relatively immobile. In patients with constipation abdominal distension can occur. Frequently patients will have left iliac fossa pain. Dilated loops would not be typical and faecal loading may be seen in the colon. Diverticulitis Diverticulitis refers to inflammation of diverticulae, which are most frequently found in the sigmoid colon. It normally presents with left iliac fossa pain and fever, possibly with PR bleeding. Inflammatory markers would be elevated, although in this instanc e these are more likely to be explained by the already diagnosed lower respiratory tract infection. Small bowel obstruction Small bowel obstruction usually presents with vomiting, absolute constipation, and painful abdominal distension. The commonest causes are intra-abdominal adhesions and hernias, other causes include foreign bodies, gallstone ileus, volvulus, neoplasms and strictures (eg from previous ischaemia or from Crohn’s disease). In small bowel obstruction you will usually see dilated small bowel loops proximal to the point of obstruction.

Answer 246

Explanation Postprandial pain, vomiting and dizziness Dumping syndrome following gastrectomy is due to an absent gastric reservoir, abnormal postoperative gastric motor function and hormonal secretion alteration. After eating, symptoms are related to the rapid transit of hyperosmolar contents into the small bowel. It can be split into early dumping syndrome, occurring within 10–30 min after a meal, and late dumping syndrome, which occurs after 2–3 h. Early dumping syndrome results from rapid osmotic fluid shifts from the blood into the intestine resulting in decreased total blood volume and intestinal distension. Late dumping syndrome results from rapid absorption of sugar from the intestine followed by a rapid increase in insulin levels and a subsequent hypoglycaemic episode. Early dumping syndrome symptoms include abdominal pain, vomiting and nausea, diarrhoea, sweating and flushing, and dizziness. Late dumping syndrome symptoms include sweating, weakness, flushing and dizziness. Treatment is largely through managing dietary intake with several small meals a day (instead of large meals) and avoiding simple sugars. Additionally, liquids should be drunk in between meals not alongside meals. A high fibre diet can also help. Octreotide and proton pump inhibitors (PPIs) can also help to slow gastric emptying if conservative management fails. Collapse and chest pain This is not correct. Left upper quadrant pain, diarrhoea, chest pain This is not correct. Pain before eating, dizziness and nausea This is not correct, in particular symptoms occur after eating. Shortness of breath and chest pain This is not correct.

Answer 247

Explanation Bile salts Bile salts are primarily re-absorbed in the terminal ileum – loss of bile salts in faeces has several knock-on effects. Bile salts released in the bile are normally responsible for solubilising dietary fat – so excess loss of bile salts results in fat malabsorption. One important effect of this is malabsorption of the fat soluble vitamins A, D, E and K. Additionally the terminal ileum is the primary site for absorption of vitamin B 12 – loss of which results in a macrocytic anaemia. Calcium Calcium and folic acid are mainly absorbed in the jejunum. Cholesterol Dietary fat, including cholesterol, is primarily absorbed in the jejunum. However, excess loss of bile salts, which are absorbed in the ileum, can lead to fat malabsorption in the jejunum. Folic acid Calcium and folic acid are mainly absorbed in the jejunum. Sodium Sodium is re-absorbed throughout the small bowel.

Answer 248

Explanation Lack of bile salts This patient has gallstones because of a lack of bile salts which are usually involved in fat absorption. He has Crohn’s disease, which resulted in a small bowel resection. This is most commonly in the terminal ileum where bile salts are most predominantly absorbed. Bile salts aid with the absorption of fat by forming micelles. Without the presence of bile salts in bile, cholesterol will more readily sediment out to form gallstones. Other risk factors include obesity, female sex, increasing age, diabetes me llitus, and premenopausal status or use of HRT/oral contraceptives. Age Increasing age is a risk factor for developing gallstones, classically they become more likely especially above the age of 40. Diet Dietary factors are not a major risk factor for deve loping gallstones. Increased haemosiderin Haemosiderin is a complex that stores ferritin; deposits are most commonly associated with iron overload conditions, such as hereditary haemochromatosis. They are not a risk factor for gallstones. Sex Gallstones are more common in women than in men.

Answer 249

Explanation Hypochloraemic alkalosis Prolonged vomiting causes a hypochloraemic metabolic alkalosis. The reason for this is that H + and Cl – , from gastric secretions within the stomach, are lost and in addition the alkaline pancreatic and duodenal secretions are retained. The loss of H + obviously directly leads to alkalosis, however the loss of Cl – also results in retention of the other major anion in the body, HCO 3 – (bicarbonate). All together this results in a hypochloraemic metabolic alkalosis. The loss of fluid volume causes a physiological response that includes sympathetic stimulation, increase in ADH secretion and activation of the renin–angiotensin–aldosterone system. In small bowel obstruction, there is also loss of alkaline intestinal secretions, which prevents the development of metabolic alkalosis. Decreased antidiuretic hormone (ADH) secretion Loss of fluid and inability to take in oral fluids will result in dehydration and loss of intravascular fluid volume and therefore increased ADH secretion as the body tries to maintain its intravascular fluid volume. Metabolic acidosis The loss of H+ and Cl – from gastric secretions results in hypochloraemic metabolic alkalosis. Respiratory alkalosis Respiratory alkalosis results from hyperventilation and therefore excess removal of carbon dioxide from the body, while the patient will be alkalotic this is not due to a respiratory cause. Hyperkalaemia The patient will most likely become hypokalaemic. A relatively small amount of potassium will be directly lost in the vomit. However, more importantly, the pat ient will become alkalotic (metabolic alkalosis) – alkalosis results in a transcellular exchange of potassium going into the cells and hydrogen ions leaving the intracellular compartment, the increased reabsorption of H + in the kidneys also results in increased exchange of potassium into the urine. Finally the patient’s hypovolaemia and resultant increase in aldosterone production also results in loss of potassium at the kidneys.

Answer 250

Explanation Microscopic examination of a small bowel biopsy specimen The detection of the typical appearance of subtotal villous atrophy on a small bowel biopsy is regarded as the ‘gold standard’ for the diagnosis of coeliac disease. Other changes include increased numbers lymphocytes and crypt hyperplasia. Detection of antigliadin antibodies in serum Sensitivity and specificity among studies for this test is highly variable but generally less than endomysial antibodies (EMA) and tissue transglutaminase (TTG) antibodies. Detection of endomysial antibodies (EMA) in serum Sensitivity and specificity are >95% making this a very good screening test, however, biopsy remains the gold standard. Endomysial antibodies have been identified as binding to a spec ific form of tissue transglutaminase within the endomysium. Detection of tissue transglutaminase (TTG) antibodies in serum Again sensitivity and specificity are >95% therefore this test is good for screening – but biopsy is the gold standard. Xylose absorption test The xylose absorption test is a non-specific test for intestinal malabsorption.

Answer 251

Explanation Gilbert syndrome Gilbert syndrome is a common (approximately 1:2 0) autosomal-recessive cause of mild unconjugated hyperbilirubinaemia. This occurs due to defective conjugation within the liver. Normally mild jaundice develops when affected patients develop concomitant infections, are fasting or have other physiological stressors. As the hyperbilirubinaemia is unconjugated it will not be present in the urine. Dubin–Johnson syndrome Dubin–Johnson syndrome is an autosomal-recessive condition causing a conjugated hyperbilirubinaemia due to a defect in the secretion of bilir ubin from the liver. The bilirubin that then accumulates in the plasma is conjugated, water -soluble and so is excreted in the urine. One key difference between and Rotor syndrome is that in Rotor syndrome the liver is classically pigmented black. Hereditary spherocytosis Hereditary spherocytosis is a chronic haemolytic disorder due to a defect in the red -cell membrane (most frequently in spectrin, a structural protein). It can present with a wide range of severity, from jaundice at birth to asymptomatic anaemia or jaundice in adults. It is pre-hepatic jaundice and will therefore be unconjugated with no bilirubin in the urine. However, it is much less common than Gilbert’s syndrome so less likely (approximately 1:5000 in Northern Europeans). Infectious mononucleosis Infectious mononucleosis (IM) can cause hepatitis and jaundice but an elevated transaminase activity would be expected. It normally presents with a tonsillitis, general malaise, and cervical lymphadenopathy – the absence of these makes IM unlikely. Rotor syndrome Rotor syndrome is an autosomal-recessive condition, causing a conjugated hyperbilirubinaemia due to defective transporter proteins from hepatocytes into the biliary tree. As the bilirubin that accumulates in the plasma is conjugated, water-soluble and therefore excreted in the urine.

Answer 252

Explanation Pancreatic cancer Pancreatic cancer classically presents insidiously with painless jaundice, often with a history of weight loss as the cancer usually presents at late stage. These cancers tend to be cancers of the head of the pancreas as it is through this portion of the pancreas that the CBD traverses. As this is the only condition listed that typically causes painless jaundice it is the correct answer. Obstructive jaundice classically produces dark urine and paler stools and it would be usefu l to know this from the history. Biliary colic This normally presents with sudden onset, colicky right upper quadrant pain. Often associated with recent ingestion of large/fatty meals. It is unusual for jaundice to develop unless a gallstone has entered to common bile duct, or occasionally a gallstone within the neck of the gall-bladder or Hartmann’s pouch can compress the common bile duct (CBD) and cause an obstructive jaundice (known as Mirizzi’s syndrome). The absence of pain and insidious onset strongly goes against this diagnosis. Ascending cholangitis Ascending cholangitis is a medical emergency that can be recognised by Charcot’s triad of fever, right upper quadrant abdominal pain and jaundice. This insidious presentation does not fit this diagnosis. Cholecystitis Cholecystitis normally presents with constant right upper quadrant pain and fever, classically the patient is Murphy’s positive in which deep inspiration while palpating the right upper quadrant (RUQ) results in the patient ‘catching their breath’ as the inflamed gall-bladder is lowered onto the palpating hand. Jaundice is uncommon unless a stone within the neck of the gall-bladder or Hartmann’s pouch is compressing the CBD and can cause an obstructive jaundice (known as Mirizzi’s syndrome), additionally the localised inflammation and swelling around the gall- bladder can result in compression of the CBD and therefore an obstructive jaundice. Gallstone ileus Gallstone ileus occurs when a gallstone enters the small bowel, usually through a fistula connecting the gall-bladder and small intestine. It can then cause a mechanical small bowel obstruction. It does not cause jaundice.

Answer 253

Explanation Wilson’s disease Wilson’s disease is an autosomal-recessive disorder that results in the toxic accumulation of copper in the liver and central nervous system (CNS) (in particular the basal ganglia). Children often present with liver disease, and adults with CNS features. Kayser –Fleischer rings are copper deposits in the iris (Descemet’s membrane) that are pathognomic but not invariable and may require a slit-lamp to be seen. Blood tests would possibly reveal low ceruloplasmin and high serum copper, along with abnormal LFTs. First -line treatment is with d-penicillamine, a copper chelating drug, along with dietary advice on avoidance of copper -containing foods. Alcoholic cirrhosis Alcohol is a very common cause of deranged liver function tests, and can also present with confusion and ataxia as part of Wernicke’s syndrome. However, this patient is very young to have developed this already, especially without any mention of a significant alcohol history, and alcohol does not cause Kayser–Fleischer rings (which are pathognomonic of Wilson’s disease). Alpha-1 antitrypsin deficiency Alpha-1 antitrypsin deficiency is an autosomal-recessive condition that predispo ses affected patients to cirrhosis and chronic obstructive pulmonary disease (COPD) (due to a predisposition to develop emphysematous changes in the lungs), it does not have neurological affects. Autoimmune hepatitis Autoimmune hepatitis can present as an acute hepatitis or a chronic hepatitis and eventually leads to cirrhosis. It is associated with autoantibodies, including antinuclear antibody (ANA) and smooth muscle autoantibodies, it is most common in women and in those aged 40 –50 years. Additionally, it does not cause neurological disease. Hepatitis B Hepatitis B is a viral hepatitis, which in the UK is normally acquired as an adult through needle - sharing or sexual intercourse. In endemic countries the vertical transmission route is relatively much more important. In the majority (approx 95%) of those infected as adults it causes an acute infection that may be symptomatic or may cause hepatitis, but is eventually cleared successfully. The risk of chronic infection if infected perinatally at birth is ar ound 90%. Those with a chronic infection can also develop cirrhosis (approx 20%) or reactivation of the disease periodically (approx 25%). These scenarios could account this patient’s deranged LFTs, however, hepatitis B does not usually cause neurological effects and in the absence of stated risk factors hepatitis B infection is unlikely.

Answer 254

Explanation Hepatocellular carcinoma (HCC) HCC is the commonest malignant tumour of hepatocytes accounting for 90% of primary liver cancers. World-wide it is most commonly caused by chronic hepatitis B, followed by hepatitis C infection, and its incidence is highest in Asia (such as Thailand where this patient is from) and sub-Saharan Africa. In Europe, hepatitis C infection is the most common cause, however any cause of cirrhosis puts patients at increased risk of HCC – so alcoholism, autoimmune conditions such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), and genetic conditions such as haemochromatosis PBC are all common causes. Another important cause in Asia and sub-Saharan Africa is aflatoxins – these are toxins produced by fungi that contaminate foodstuff such as peanuts and grains. In the UK the incidence of HCC is around 4.3 per 100 000 (Cancer Research UK). It commonly presents on the background of cirrhosis and associated signs, possibly presenting due to a deterioration in the patient’s chronic liver disease. Other symptoms suggestive of HCC include right upper quadrant pain, weight loss, and new onset ascites/jaundice. On examination they may be palpable as an irregular hepatomegaly and sometimes a bruit may be heard over them. The a-fetoprotein levels are raised in 80% of patients. Patients at high risk of HCC should be screened every 6 –12 months with ultrasound liver and serum AFP – these patients include cirrhotic patients due to HBV/HCV, PBC, haemochromatosis and alcoholism. Cholangiocarcinoma Cholangiocarcinoma most commonly presents with jaundice and deranged liver function tests, possibly with abdominal pain, all due to obstruction of the biliary tree , often on a background of weight loss. It can also present acutely with fever, jaundice and abdominal pain due to it predisposing towards ascending cholangitis. It is a rare cancer, affecting 3.58 per 100 000 population in England (National Cancer Intelligence Network statistics for rare and less common cancers). In addition, it would be unusual for this cancer to present with a palpable mass without having caused obstruction and resultant jaundice. Fibrosarcoma of the liver Fibrosarcomas are tumours arising from fibroblasts. They are most common in the limbs, but even then are uncommon. The literature regarding these tumours affecting the liver is confined to only a few case reports in which they tend to present as large masses. The most common type of sarcoma affecting the liver is the angiosarcoma, which makes up around 0.3% of all liver cancers (Cancer Research UK statistics). Gallstones Gallstones normally present in the context of biliary colic – sudden onset, colicky right upper quadrant pain. Often associated with recent ingestion of large/fatty meals. They would not explain the bruit, or the palpable irregular hepatomegaly, nor the raised AFP or weight loss. Liver haemangioma These are the most common benign liver tumour, mostly they are incidental findings on imaging for other indications, if they do present clinically it is normally with a right upper quadrant (RUQ) ‘fullness’ or pain – they would not, however, cause this patient’s weight loss or raised AFP.

Answer 255

**Answer: 4) Ulcerative colitis** **Explanation:** The sigmoidoscopy findings of **inflamed mucosa** and the rectal biopsy showing **goblet-cell depletion**, **crypt abscesses**, and **inflammatory infiltrate** are classic histological features of **ulcerative colitis (UC)**. UC is characterized by: - **Continuous mucosal inflammation** starting in the rectum and extending proximally. - **Crypt abscesses** (neutrophils infiltrating crypts). - **Goblet-cell depletion** due to chronic mucosal damage. - **No granulomas or transmural inflammation** (which would suggest Crohn’s disease). **Exclusion of Other Options:** 1. **Coeliac disease**: Affects the **small intestine** (villous atrophy), not the rectum. 2. **Crohn’s disease**: Typically causes **transmural inflammation**, skip lesions, and granulomas; rectal involvement is less common. 3. **Irritable bowel syndrome (IBS)**: A **functional disorder** without structural or inflammatory changes on biopsy. 5. **Whipple’s disease**: Rare systemic infection with **PAS-positive macrophages** in the small intestine, not the rectum. **Conclusion:** The clinical, endoscopic, and histological findings strongly support **ulcerative colitis** as the diagnosis.

Answer 256

Explanation Crohn’s disease Crohn’s disease is a form of inflammatory bowel disease that has several features in common with ulcerative colitis and commonly presents between 10 –40 years of age. However, it is characterised by transmural granulomatous inflammation and can affect any part of the gut. It is most commonly found in the terminal ileum (and therefore may produce discomfort in the RIF), but can affect anywhere from mouth to anus causing discontinuous skip lesions. Other features seen include diarrhoea and weight loss. Perianal disease is also common and may manifest as abscesses and fistulae. Barium enemas will classically show cobblestoning and ‘rose -thorn’ ulcers. A magnetic resonance imaging (MRI) scan can also be used to assess the extent of pelvic disease. Endoscopy may reveal deep ulceration and a cobblestone appearance, fissures, abscesses and stenosis are frequent findings. Histologically there may be an inflammatory infiltrate, non - caseating granulomas and transmural inflammation. Coeliac disease Coeliac disease is a condition that affects the small bowel – chronic inflammation results from autoimmune reaction to gluten, with serum findings of antiendomysial, antitissue transglutaminase and antigliadin antibodies. It results in diarrhoea, normally without blood, abdominal pain and bloating, and malabsorption. Endoscopic findings in the small bowel include villous atrophy, increased numbers of lymphocytes and crypt hyperplasia. Irritable bowel syndrome Irritable bowel syndrome (IBS) presents with long -term altered bowel function, such as diarrhoea or constipation or alternation between the two, often with abdominal pain or bloating. It is a functional condition, by definition with no discernible metabolic or mechanical cause – signs or symptoms such as bloody diarrhoea, anaemia, weight loss, and evidence of malabsorption all point firmly away from this diagnosis. Whipple’s disease Whipple’s disease is caused by infection with Tropheryma whipplei, commonly it presents with diarrhoea (steatorrhoea) and weight loss as a result of malabsorption. Joint pain and arthritis are also common, usually a migratory non-deforming arthritis. Less common but recognised features also include skin pigmentation, endocarditis, uveitis and CNS involvement. Diagnosis is made by endoscopy of the duodenum, and biopsy showing PAS -positive macrophages and non-acid- fast Gram-positive bacilli. Ulcerative colitis Ulcerative colitis commonly presents between the ages of 15 and 30 years. It is characterised by diarrhoea often with mucus and blood. There may be a crampy abdominal pain, and the frequency of motions may be related to the severity of an attack. It may affect only the rectum (proctitis in approximately 50%), or spread proximally to involve part or the rest of the colon. Barium enema reveals button-shaped ulcers and pseudopolyps, thickened bowel-wall and haustra, filiform polyps and, in cases of chronic inflammation, a ‘lead pipe’ colon can occur (featureless colon with no normal haustral markings). Sigmoidoscopy shows an inflamed and friable mucosa from the rectum and a variable but continuous amount proximally. Histologically there may be an inflammatory infiltrate, goblet -cell depletion, glandular distortion, mucosal ulcers and crypt abscesses.

Answer 257

Explanation Chronic pancreatitis Chronic pancreatitis presents most commonly either with chronic epigastric pain, or multiple episodes of acute epigastric pain, often radiating into the back. The pain may be relieved by sitting forwards and is often made worse by eating. Patients may also report nausea and vomiting, bloating and pale/difficult to flush/malodourous stools (steatorrhoea) with weight loss. The later symptoms are a result of pancreatic exocrine insufficiency resulting in malabsorption. The patient may also have signs/symptoms of endocrine insufficiency resulting in high body mass (BM), with polyuria and polydipsia. The commonest cause of chronic pancreatitis is alcohol excess, while gallstones is another common cause. It can also idiopathic, due to trauma, autoimmune disease, cystic fibrosis or other genetic disorders. There are a number of features of this case to suggest it is chronic pancreatitis rather than acute – its prolonged history and the patient has symptoms suggestive of steatorrhoea from exocrine insufficiency. The presence of erythema ab igne also fits with a chronic picture. This is a ‘rash’ consisting of reticular erythema and hyperpigmentation most often caused by chronic use of a hot water bottle to relieve pain and is often seen in the epigastrium or on the back. Acute pancreatitis Acute pancreatitis classically presents with sudden onset of severe epigastric pain radiating through to the back, better on sitting forwards. Commonly patients will be nauseous and vomiting, and have evidence of localised peritonitis (such as rebound tenderness and guarding in the epigastrium). The most common causes are gallstones and excessive alcohol, other causes can be remembered by the mnemonic below. While the description of the pain suffered by the patient is certainly fitting with pancreatitis, there are several features that point towards chronic rather than acute pancreatitis – including the multiple episodes over several weeks, and the evidence of exocrine insufficiency causing steatorrhoea. Biliary colic This normally presents with sudden onset, colicky right upper quadrant pain. Often associated with recent ingestion of large/fatty meals. The site of the pain in this patient does not fit with this description, and biliary colic would not explain his stools. Coeliac disease Coeliac disease is a condition that affects the small bowel – chronic inflammation results from autoimmune reaction to gluten, with serum findings of anti-endomysial, anti-tissue transglutaminase and anti-gliadin antibodies. It results in diarrhoea (normally without blood), abdominal pain, bloating, weight loss, fatigue and mouth ulcers. In addition commonly malabsorption is present which may manifest as iron-deficiency anaemia or vitamin B12 /folate deficiency with macrocytic anaemia, or steatorrhoea (as in this patient). The severe pain, radiating into the patient’s back and in multiple distinct episodes does not fit with coeliac disease which tends to present with a milder colicky abdominal pain, or indigestion-type pain. Pancreatic Cancer Pancreatic cancer classically presents insidiously with painless jaundice. These cancers tend to be cancers of the head of the pancreas as it is through this portion of the pancreas that the common bile duct (CBD) traverses. Other symptoms of pancreat ic cancer (of any anatomical position) are general malaise, poor appetite, significant weight loss, and epigastric abdominal pain or lower thoracic back pain. Multiple severe episodes of epigastric pain without a history of weight loss/malaise do not fit well with pancreatic cancer.

Answer 258

The most likely diagnosis for a 22-year-old woman with vague abdominal pain, bloating, weight loss, offensive stools that are difficult to flush (steatorrhea), and jejunal biopsy findings of **crypt hyperplasia** and **subtotal villous atrophy** is **2) Coeliac disease**. ### Explanation: 1. **Clinical features**: - Weight loss, abdominal pain, bloating, and steatorrhea are classic symptoms of malabsorption. - Offensive stools that are difficult to flush suggest fat malabsorption, which is common in coeliac disease due to damage to the small intestinal mucosa. 2. **Jejunal biopsy findings**: - **Crypt hyperplasia** and **subtotal villous atrophy** are hallmark histological features of coeliac disease. These changes occur due to an immune-mediated reaction to gluten, leading to inflammation and flattening of the villi, which impairs nutrient absorption. ### Why not the other options? 1. **Bacterial overgrowth**: This can cause malabsorption and bloating but does not typically cause subtotal villous atrophy or crypt hyperplasia. 2. **Crohn's disease**: While Crohn's disease can cause malabsorption and weight loss, it is more commonly associated with patchy inflammation, ulceration, and granulomas, not subtotal villous atrophy. 3. **Ulcerative colitis**: This primarily affects the colon and does not cause small intestinal villous atrophy. 4. **Tropical malabsorption**: This can cause villous atrophy but is more common in tropical regions and is associated with infectious causes (e.g., tropical sprue). Coeliac disease is more likely in this case given the clinical context. ### Conclusion: The combination of symptoms, steatorrhea, and jejunal biopsy findings strongly points to **coeliac disease** as the most likely diagnosis. Confirmation can be made with serological testing (e.g., anti-tissue transglutaminase antibodies) and response to a gluten-free diet.

Answer 259

The most likely diagnosis for this 45-year-old woman with dysphagia, Raynaud’s phenomenon, radial furrowing of the lips, and tapered fingers is **4) Scleroderma** (specifically, systemic sclerosis). ### Explanation: 1. **Key Features**: - **Dysphagia**: A common symptom in systemic sclerosis due to esophageal involvement, where fibrosis and smooth muscle atrophy impair esophageal motility. - **Raynaud’s phenomenon**: A hallmark of systemic sclerosis, caused by vascular dysfunction. - **Radial furrowing of the lips** and **tapered fingers**: These are classic physical findings in systemic sclerosis, reflecting skin thickening and fibrosis. 2. **Why Not Other Options**: - **1) Achalasia**: Causes dysphagia but is not associated with Raynaud’s phenomenon or skin changes. - **2) Myasthenia gravis**: Can cause dysphagia due to muscle weakness but is not associated with Raynaud’s phenomenon or skin changes. - **3) Oesophageal carcinoma**: Typically presents with progressive dysphagia and weight loss, but there is no association with Raynaud’s phenomenon or skin changes. - **5) Syringobulbia**: A rare condition affecting the brainstem, which can cause dysphagia but is not associated with Raynaud’s phenomenon or skin changes. ### Conclusion: The combination of dysphagia, Raynaud’s phenomenon, and characteristic skin changes (radial furrowing of the lips and tapered fingers) strongly suggests **systemic sclerosis (scleroderma)**. Further evaluation, such as esophageal manometry or serological testing (e.g., anti-centromere or anti-Scl-70 antibodies), can confirm the diagnosis.

Answer 260

Explanation Haemangioma Haemangiomas are the commonest benign tumour of the liver and mostly remain asymptomatic. If they are very large (>5 cm) there is a risk of abdominal pain and rupture with intra -abdominal haemorrhage. Single-photon emission CT scan (SPECT) with 99 Tc m -labelled red blood cells will demonstrate persistence of blood activity in the lesion. Cholangiocarcinoma Cholangiocarcinoma is a malignant lesion of the biliary tree, whereas this case describes the lesion within the liver parenchyma. Haemangiosarcoma Haemangiosarcoma is a rare malignant lesion of the liver, more commonly seen in dogs than humans. Hepatocellular carcinoma Hepatocellular carcinoma is a malignant lesion of the liver. It is the most common form of liver cancer, has a strong association with chronic liver disease, and are often multifocal at diagnosis so prognosis is guarded. Hepatic adenoma Hepatic adenomas are rare benign lesions of the liver and typically present in younger women, often on the background of elevated levels of oestrogen for example from the combined oral contraceptive pill.

Answer 261

Explanation Oesophageal carcinoma Presenting features of oesophageal carcinoma are classically progressive dysphagia (initially solids and then liquids), associated with significant weight loss. Retrosternal chest discomfort may occur. The most common forms of oesophageal cancer are squamous and adenocarcinoma. Adenocarcinoma now exceeds squamous carcinoma by a ratio of 2:1. The ratio was previously in the reverse direction. Achalasia Achalasia is a motility disorder of the oesophagus in which relaxation of the lower oesophageal sphincter fails preventing passage of food into the stomach. It presents with progressive dysphagia and regurgitation of undigested food Barrett’s oesophagus Adenocarcinoma is predisposed to by a metaplastic change in the oesophageal mucosa from squamous to columnar epithelium by chronic reflux (Barrett’s oesophagu s). However, in this case there is no history of reflux disease. Hiatus hernia A hiatus hernia is likely to result in reflux symptoms and retrosternal pain, it would not cause dysphagia and weight loss. Pharyngeal pouch A pharyngeal pouch is a diverticulum through Killian’s dehiscence. It presents with halitosis, dysphagia and regurgitation. It is common in elderly men, however significant weight loss would not necessarily be expected as described in the case above.

Answer 262

Explanation Scleroderma The colour change describes the classic pattern in Raynaud’s syndrome. This may be idiopathic, or associated with connective tissue disorders, vascular obstructive disorders or occupation. In this case, the patient has scleroderma. Calcinosis cutis, Raynaud’s phenomenon, oesophophageal dysfunction, sclerodactyly and telangiectasia syndrome (CREST) syndrome is a form of scleroderma. Its five main features are associated with anticentromere antibodies. Achalasia Achalasia is a motility disorder of the oesophagus in which relaxation of the lower oesophageal sphincter fails, preventing passage of food into the stomach. It presents with progressive dysphagia and regurgitation of undigested food. Diffuse oesophageal spasm Diffuse oesophageal spasm causes intermittent chest pain upon eating food as the oesophagu s spasms against a food bolus. It can be very painful but would not cause true dysphagia or lip changes. Myasthenia gravis Myasthenia gravis is an autoimmune condition due to antibodies against the acetylcholine receptors of the neuromuscular junction. It results in progressive muscle fatigue. There is no association with Raynaud’s phenomenon and lip changes. Oesophageal carcinoma Oesophageal carcinoma classically presents with progressive dysphagia (initially solids and then liquids). This is often associated with significant weight loss. Retrosternal chest discomfort may also occur. The key features in this history to differentiate are skin colour changes and lip changes.

Answer 263

Gastric cancer Gastric cancer often starts with very non-specific symptoms – anorexia, weight loss, features of dyspepsia. Tumours of the antrum can cause gastric outlet obstruction and present with fullness, nausea and vomiting. Features found on examination can include signs of metastases – ascites, irregular hepatomegaly and Virchow’s node (a hard lymph node in the left supraclavicular fossa). Duodenal ulcer While a duodenal ulcer may present with vague abdominal pain, there is unlikely to be significant weight loss and irregular hepatomegaly would not be seen. Gallstones Gallstones will result in right upper quadrant abdominal pain that is wor se when consuming fatty meals. Virchow’s node is indicative of an intra-abdominal malignancy. Gastro-oesophageal reflux disease (GORD) GORD would not present with weight loss or irregular hepatomegaly. It is a common condition resulting in indigestion that is worse after food and upon lying down. Gastric ulcer An ulcer would not cause irregular hepatomegaly or significant weight loss.

Answer 264

The most likely cause of haematemesis in this 17-year-old man with extensive burns is **1) Curling’s ulcer**. ### Explanation: 1. **Curling’s Ulcer**: - This is a stress ulcer that occurs in patients with **severe burns**, typically involving >30% of total body surface area. - It is caused by **hypovolaemic shock**, reduced splanchnic blood flow, and increased gastric acid secretion following major burns. - It usually presents **5–14 days after the burn injury**, which aligns with the timeline in this case (6 days post-burn). 2. **Why Not Other Options**: - **2) Cushing’s ulcer**: This is a stress ulcer associated with **head injury** or **raised intracranial pressure**, not burns. - **3) Oesophageal burns**: These would present immediately after the injury, not 6 days later. - **4) Mallory-Weiss tear**: This is caused by forceful vomiting and retching, often in the context of alcohol abuse or bulimia, and is not specifically related to burns. - **5) Zollinger-Ellison syndrome**: This is a rare condition caused by a gastrin-secreting tumor, leading to severe peptic ulcer disease, but it is not associated with burns. ### Conclusion: The development of haematemesis 6 days after extensive burns is most consistent with **Curling’s ulcer**. Management includes proton pump inhibitors (PPIs), endoscopic evaluation, and treatment of the underlying burn injury. .

Answer 265

Explanation Gastrointestinal cancer The skin changes described in this case is acanthosis nigricans and is associated with gastrointestinal (eg stomach) cancer. Rheumatoid arthritis Rheumatoid arthritis is an autoimmune condition resulting in inflammation of the synovium causing joint pain and swelling. Cutaneous manifestations include palmar erythema, skin atrophy, and brittle nails. Coeliac disease Coeliac disease is associated with dermatitis herpetiformis in which itchy blisters develop over the knees, elbows and scalp. Crohn’s disease Crohn’s disease is associated with several skin changes including pyoderma gangrenosum and erythema nodosum. Chronic pancreatitis Cutaneous manifestations of chronic pancreatitis are uncommon and often examination is unremarkable except for vague abdominal pain.

Answer 266

Explanation Iron and vitamin B 12 deficiency are common Surgery for morbid obesity is considered in individuals who have a body mass index (BMI) more than 40 kg/m 2 . Obesity surgery for patients with a body mass index (BMI) between 35 –39 kg/m 2 may be justified if they have a co -morbid condition that will be improved by weight loss. The decision to operate must be made within a dedicated multidisciplinary team comprising a bariatric surgeon, dietician, physician, anaesthetist, radiologist and clinical nurse specialist. the conditions that can be improved by weight loss include type II diabetes mellitus, hypertension and dyslipidaemia (the metabolic syndrome). Others include obstructive sleep apnoea, decreased mobility, osteoarthritis and hypertrophic cardiomyopathy and poor quality of life. Importantly, it must be remembered that gastric bypass surgery can result in iron and vitam in B 12 deficiencies. Perioperative mortality associated with bariatric surgery is 3% and is an important consideration that should be discussed with the patient before surgery Perioperative mortality for bariatric surgery is reported as less than 0.3% and is declining due to improved management in specialist bariatric centres with multidisciplinary care. Complications of surgery should always be discussed with the patient; in bariatric surgery patient expectations around weight loss following surgery can be unrealistic and must be managed. An adjustable gastric band forms an integral part of the procedure The surgery can be broadly classified into restrictive and malabsorptive. The former consists of gastric banding or vertical banded gastroplasty which reduces the size of the stomach. The latter is achieved by bypass procedures to alter the digestive tract so that less absorption occurs. Most procedures are a combination of the two techniques. Jejuno-ileal bypass with cholecystectomy is the preferred option Jejuno-ileal bypass has fallen from favour as it has been associated with serious complications. Weight loss from a biliopancreatic diversion with duodenal switch is less effective than biliopancreatic diversion alone A combined surgical approach of biliop ancreatic diversion with duodenal switch is associated with greater weight loss.

Answer 267

bleeding. The Blatchford score, which has been shown to predict the risk of requiring intervention (transfusion, endoscopic or surgical therapy) and the Rockall score, which predicts the risk of re-bleeding and death. Below is a table showing the Rockall score. The scores are summed, the higher the score the higher the risk of re-bleeding and the higher the risk of mortality. Admission scores 0 points 1 points 2 points 3 points Age <60 60–79 80+ – Shock SBP >100, pulse <100 SBP >100, pulse >100 SBP <100, pulse >100 – Comorbidities None None CCF, IHD or other major comorbidity Renal or liver failure, disseminated malignancy Postendoscopy 0 points 1 points 2 points 3 points Diagnosis Mallory–Weiss tear, no lesion All other diagnoses Malignancy of upper GI tract – Major stigmata None or dark spot only – Blood, adherent clot, visible or bleeding vessel – As you can see from the scoring system – the most important factors in predicting re-bleeding are: the presence of significant endoscopic stigmata of recent haemorrhage with a visible bleeding vessel, haemodynamic instability or shock, malignancy of the up per GI tract, age over 60 years and certain comorbidities. The Blatchford score also includes systolic blood pressure and pulse, hepatic disease and cardiac failure, and additionally includes admission haemoglobin, urea, melaena, syncope. Age Age of 60 years or above does predict re-bleeding risk, however, this patient is <60 years old. Blood pressure This patient's blood pressure is within the normal range – while a low blood pressure does predict increased re-bleeding risk, a normal blood pressure does not. Ulcer size Ulcer size does not influence re-bleeding risk according to the major guidelines and scoring systems. Urea This option is part of the Blatchford scoring system that predicts the need for intervention, but has not been shown to predict re-bleeding risk, we do not know this patient’s urea levels so cannot comment any further on it.

Answer 268

Explanation 15% Around 10–15% of gallstones can be seen on plain imaging due to calcification of the stones. These often appear as rings due to calcium deposition around a central organic core. In some cases the gall-bladder may be calcified (‘porcelain gall-bladder’) and therefore visible. Porcelain gall-bladder is a type of chronic cholecystitis, its presence increases the risk of developing gall- bladder cancer and cholecystectomy is the usual treatment. The most common imaging modality used to detect gallstones is abdominal ultrasound – this has a much higher sensitivity of 85%, and specificity up to 100%. <1% The correct answer is 10–15%. 30% Gallstones are not usually visualised with abdominal X-ray (AXR). 50% As above, however renal stones tend to be more radio -opaque. >75% This is an incorrect response.

Answer 269

Explanation Zollinger-Ellison syndrome Zollinger–Ellison syndrome is the constellation of multiple, usually severe, peptic ulcers affecting the stomach and duodenum associated with a gastrinoma (a tumour of gastrin-secreting ‘G’ cells, usually in the pancreas but can also be in the stomach or duodenum). Excess gastrin promotes excess gastric acid secretion – this acid leads to peptic ulceration, and diarrhoea is a common symptom too. Patients complain of epigastric pain due to peptic ulceration which may be better with food. Around one-third of patients have MEN-1syndrome. Curling’s ulcer A Curling’s ulcer is a stress ulcer within the stomach or duodenum that occurs acutely in association with severe skin burns. They are usually multiple and shallow. Cushing’s ulcer A Cushing’s ulcer is an ulcer within the stomach or duodenum associated with raised intracranial pressure – raised intracranial pressure classically presents with headaches that are worse in the morning and on lying down, associated with nausea and blurred vision. Duodenal carcinoma Duodenal carcinoma is uncommon [only 0.3% of gastrointestinal (GI) malignancies], it is usually an adenocarcinoma and could present as an ulcerated lesion, commonly it presents with abdominal pain, as well as weight loss, nausea and vomiting, or with bleeding. It is unlikely to present as multiple small erosions as described here though, and most commonly presents in the sixth decade of life. VIPoma This is a rare type of cancer of the pancreatic islets that results in secretion of vasoactive intestinal peptide (VIP). It primarily presents with watery diarrhoea, that can result in hypokalaemia and dehydration. It is sometimes associated with multiple endocrine neoplasia type 1 (MEN1).

Answer 270

Explanation Hepatocellular carcinoma (HCC) HCC is the commonest malignant tumour of hepatocytes accounting for 90% of primary liver cancers. It usually occurs on a background of cirrhosis, world-wide it is most commonly caused by chronic hepatitis B, followed by hepatitis C infection, and its incidence is highest in Asia and sub-Saharan Africa. In Europe, hepatitis C infection is the most common cause, however, any cause of cirrhosis puts patients at increased risk of HCC – so alcoholism, autoimmune conditions such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), and genetic conditions such as haemochromatosis are all common causes. Another important cause in Asia and sub-Saharan Africa is Aflatoxins – these are toxins produced by fungi contaminating foodstuff such as peanuts and grains. In the UK the incidence of HCC is around 4.3 per 100 000 (Cancer Research UK). It commonly presents on the background of cirrhosis and associated signs, possibly presenting due to a deterioration in the patient’s chronic liver disease, for example with encephalopathy, ascites and reduced synthetic function. Other symptoms suggestive of HCC include right upper quadrant pain, weight lo ss, and new onset ascites/jaundice. On examination they may be palpable as an irregular hepatomegaly and sometimes a bruit may be heard over them. The a-fetoprotein levels are raised in 80% of patients. Increasingly patients are also detected on screening in the UK. Patients at high risk of HCC should be screened every 6–12 months with ultrasound liver and serum AFP – these patients include cirrhotic patients due to HBV/HCV, PBC, haemochromatosis and alcoholism (see BSG Guidelines for more information). Cholangiocarcinoma Cholangiocarcinoma most commonly presents with jaundice and deranged liver function tests, possibly with abdominal pain, all due to obstruction of the biliary tree, often on a background of weight loss. It can also present acutely with fever, jaundice and abdominal pain due to it predisposing towards ascending cholangitis. It is a rare cancer, affecting 3.58 per 100 000 population in England (National Cancer Intelligence Network statistics for rare and less common cancers). Fibrolamellar carcinoma Fibrolamellar carcinoma is a rare variant of HCC, around 1:5 million population incidence, affecting children and young adults without a history of background liver disease. Risk factors remain poorly understood. Haemangioma These are the most common benign liver tumour, mostly they are incidental findings on imaging for other indications, if they do present clinically it is normally with a RUQ ‘fullness’ or pain – they would not, however, cause this patient’s signs of decompensated liver disease. Hepatic angiosarcoma This cancer makes up around 2% of primary liver cancers, originating from endothelial cells within the liver. It usually presents with a mass and general signs such as weight loss and malaise. It can also present with rupture and bleed ing. Risk factors include environmental toxins, such as vinyl chloride or arsenic.

Answer 271

The correct symptom associated with **chronic alcohol abuse** in this scenario is: **2) Menstrual disturbance** ### Explanation: Chronic alcohol abuse can lead to a wide range of physical, psychological, and hormonal disturbances. Among the options provided: 1. **Menstrual disturbance**: Chronic alcohol use can disrupt the hypothalamic-pituitary-gonadal axis, leading to hormonal imbalances. This can result in irregular menstrual cycles, amenorrhea (absence of menstruation), or other menstrual disturbances. 2. **Other symptoms of chronic alcohol abuse** (not listed in the options but relevant to the case): - **Upper abdominal pain**: Often due to alcoholic hepatitis, pancreatitis, or gastritis. - **Nausea, vomiting, and retching**: Common in alcohol withdrawal or due to gastritis. - **Low mood**: Alcohol is a depressant and can exacerbate or cause depression. - **Liver damage**: Leading to jaundice, ascites, or coagulopathy. - **Neuropathy**: Peripheral nerve damage due to alcohol toxicity or vitamin deficiencies. - **Macrocytosis**: Enlarged red blood cells due to folate or vitamin B12 deficiency (not microcytosis). ### Why not the others? 1. **Heightened libido**: Chronic alcohol abuse is more likely to reduce libido due to hormonal imbalances and general health decline. 3. **Microcytosis**: This is typically associated with iron deficiency anemia, not chronic alcohol abuse. Alcohol abuse is more likely to cause **macrocytosis** due to folate or vitamin B12 deficiency. 4. **Primary thrombocythemia**: This is a myeloproliferative disorder unrelated to alcohol abuse. 5. **Sydenham’s chorea**: This is a neurological disorder associated with rheumatic fever, not alcohol abuse. ### Conclusion: The symptom most directly associated with chronic alcohol abuse in this list is **menstrual disturbance**.

Answer 272

Explanation Cholangitis Ascending cholangitis is a medical emergency that can be recognised by Charcot’s triad of fever, right upper quadrant abdominal pain and jaundice. It is caused commonly by biliary obstruction that promotes biliary stasis and allows for infection to ascend from the duodenum. The commonest risk factor is a gallstone but other causes include pancreatic head cancer or cholangiocarcinoma, strictures, stents or recent endoscopic retrograde cholangiopancreatography (ERCP). Patients can become very unwell with cholangitis and develop sepsis and subsequent septic shock. Treatment involves intravenous (IV) antibiotics, fluid resuscitation and an ERCP to relieve the biliary obstruction. Biliary colic This normally presents with sudden onset, colicky right upper quadrant pain. Often associated with recent ingestion of large/fatty meals. It is unusual for jaundice to develop unless a gallstone has entered to common bile duct, or occasionally a gallstone within the neck of the gall-bladder or Hartmann’s pouch can compress the CBD and cause an obstructive jaundice (known as Mirizzi’s syndrome). Additionally, patients are not usually tender in the RUQ (although this is where the pain is lo cated) and they should not be febrile. Cholecystitis Cholecystitis normally presents with constant right upper quadrant pain and fever, classically the patient is Murphy’s positive where deep inspiration while palpating the RUQ results in the patient ‘catching their breath’ as the inflamed gall-bladder is lowered onto the palpating hand. Jaundice is uncommon unless a stone within the neck of the gall-bladder or Hartmann’s pouch is compressing the common bile duct (CBD), which can cause an obstructive jaund ice (known as Mirizzi’s syndrome), additionally the localised inflammation and swelling around the gall - bladder can result in compression of the CBD and therefore an obstructive jaundice. Because jaundice is unusual this is not the most likely cause of this presentation. Gallstone ileus Gallstone ileus occurs when a gallstone enters to small bowel, usually through a fistula connecting the gall-bladder and small intestine. It can then cause a mechanical small bowel obstruction. It does not cause jaundice or fevers, tenderness would not be localised to the RUQ. Renal colic Renal colic is caused by renal stones within the urinary tract – it presents with severe colicky loin-to-groin pain, normally with blood on urine dipstick. Fevers do not occur except in superadded infection. The patient may be tender in the renal angle, but should not be tender in the RUQ. This certainly would not cause jaundice.

Answer 273

Explanation Anal fissure The history in the case is quite classical for an anal fissure where pain is the dominant symptom. Normally there is severe sharp anal pain on passing stool, with a burning pain afterwards. A small amount of blood on wiping may then occur, though is not always present. Examination should reveal an anal fissure, and exclude the other causes mentioned here. Common risk factors are constipation and hard stools, and Crohn's disease. Anal fistula An anal fistula is a connection between the anal canal and the perianal skin. Most commonly they result secondary to perianal abscesses, though they can also be secondary to Crohn’s disease, trauma, or cancer, among other causes. They can present with pain, itching, loc alised swelling, or discharge of pus. The absence of preceding history, and the predominance of pain at defecation makes anal fistula less likely diagnosis. Haemorrhoids These may be asymptomatic, or present with itching/irritation, bright painless bleedi ng per rectum (PR), or a feeling of ‘fullness’. Pain is not common unless the haemorrhoids are strangulated or thrombosed, in which case the pain will be severe and constant (not just when passing stool). Perianal abscess Perianal abscess presents normally with perianal pain and swelling, it may be worse when passing stool but will normally be present at other times too. Bleeding is not a common symptom. They are not related to constipation. Pilonidal sinus Pilonidal sinuses are normally present in the nat al cleft – they can be asymptomatic, or present as a small non-tender pit or lump. They may also present as a painful and tender lump, possibly with purulent discharge as an acute pilonidal abscess. Symptoms are not usually related to passing stool, and bleeding is not a common symptom, the major risk factors include hirsutism and poor personal hygiene.

Answer 274

Explanation Pilonidal abscess The commonest site for pilonidal abscesses is the natal cleft and there may be a history of recurrent episodes over months or years. Pilonidal means ‘hair’s nest’ in Latin and theories regarding its aetiology involve shed hairs getting trapped in pits and becoming a nidus for local infection. Clinically there may be openings in the midline or either side of it sometimes with tufts of hair. There may be inflammation of the adjacent skin and pus may be expressed via the openings. Management involves incision and drainage of the abscess and then other procedures can be done electively to try and prevent recurrence. Antibiotics are indicated if systemic signs of infection, or evidence of surrounding cellulitis is present. Ischiorectal abscess The ischiorectal (or ischioanal) fossae are prism-shaped fascia-lined potential spaces adjacent to the rectum. They are bordered by the levator ani muscle (superiorly and medially), the anal canal (medially), the perineal skin (inferiorly), and the ischial tuberosity (later ally). Ischiorectal abscesses are the second most common type of anorectal sepsis (30% of anorectal abscesses), after perianal abscess. Like other anorectal abscesses the pain is predominantly perianal, and often worse just before/during bowel movements – the anatomical description of this patient's abscess does not fit with this diagnosis. Hidradenitis suppurativa This is a long-term condition with multiple abscesses caused by infections within sweat glands, they are most commonly found under the arm pits, around the buttocks and groin. As well as normally having multiple lesions, the chronicity of the condition normally means that there is evidence of old abscesses, such as scarring of the skin. This is unlikely because of the single lesion this patient suffers from. Perianal abscess Perianal abscesses are the commonest form of anorectal abscess (60% of total – and present normally with perianal pain and swelling), it may be worse when passing stool but will normally be present at other times too. They are frequently recurrent, as in this patient, but the description of its location fits better with pilonidal abscess. Supralevator abscess This describes an abscess that forms from an upward extension of an intersphincteric abscess into the supralevator space. They may also form from an intra-abdominal inflammation (eg appendicitis) tracking down. They are very uncommon making up only 4% on anorectal abscesses. Like other anorectal abscesses the pain is predominantly perianal, and often worse just before/during bowel movements – as well as being a very uncommon diagnosis, the anatomical description of this patient's abscess does not fit with this diagnosis.

Answer 275

Explanation Irritable bowel syndrome Irritable bowel syndrome (IBS) is one of the commonest causes of abdominal pain and is a functional disorder with no discernible metabolic or mec hanical cause resulting in a mixture of pain, discomfort, bloating and altered bowel habit. It does not cause per rectum (PR) bleeding or mucus, or weight loss and these symptoms are suggestive of organic pathology and should be investigated appropriately and not attributed to IBS. National Institute of Clinical Excellence (NICE) recommend FBC, ESR and CRP and a coeliac screen, although other bloods and imaging are unnecessary unless there are signs/symptoms concerning for organic disease. Certainly, a colonoscopy done in a patient IBS will show a normal rectum and colon, and treatment focuses on symptomatic relief through dietary measures, antispasmodics and psychological approaches. Coeliac disease Coeliac disease is an autoimmune inflammatory condition of the small bowel caused by ongoing gluten exposure. Symptoms include abdominal bloating and pain, diarrhoea, weight loss and signs of malabsorption – this may commonly include steatorrhoea or anaemia (iron deficiency, or vitamin B 12 or folate deficiency). Colonoscopy would be normal, although small bowel biopsy would reveal villous atrophy, crypt hyperplasia and increased numbers of lymphocytes. Bloods tests typically show autoantibodies (anti-tTG, anti-gliadin and anti-endomysial), anaemia, and possibly raised inflammatory markers – a coeliac screen is recommended by the National Institute of Clinical Excellence (NICE) Guidance on inflammatory bowel disease (IBS) before making the diagnosis of IBS. Crohn’s disease This classically presents with abdominal pain, often in the right iliac fossa (as the terminal ileum is the most frequently affected segment of bowel) and non-bloody diarrhoea, weight loss and general malaise are also likely. On examination the patient is likely to have abdominal tenderness. Colonoscopy may be normal, as Crohn’s can affect any site of the alimentary canal, classically causing skip lesions. Perianal disease (fistulae, abscesses, fissures) and mouth ulcers are also common. Bloods tests may reveal anaemia, in particular a macrocytic a naemia due to vitamin B 12 malabsorption if the terminal ileum is involved – additionally, evidence of inflammation is likely on the patient’s blood tests. Hiatus hernia Hiatus hernia describes herniation of the stomach through the diaphragm – it is normally asymptomatic but can present with symptoms of gastro -oesophageal reflux disease (GORD) (indigestion/heart burn, nocturnal cough, acid brash). Blood tests and colonoscopy would be normal, but it would not usually cause the patient’s abdominal symptoms. Ulcerative colitis This classically presents with abdominal pain and tenderness with bloody diarrhoea, weight loss and general malaise. Ulcerative colitis (UC) affects the rectum, and a variable but continuous amount of colon proximal to this. Colonoscopy would therefore not be expected to be normal with ongoing symptoms as in this case. Bloods tests would also likely be abnormal, revealing raised inflammatory markers.

Answer 276

Explanation Colonoscopy This 46-year-old man requires a lower gastrointestinal (GI) endoscopy for his red flag symptoms of change in bowel habit associated with per rectum (PR) bleeding. This test is the best investigation as it allows inspection of the bowel mucosa, biopsy if required and is potentially even therapeutic, for example, if a polyp is seen this can be removed by snare and sent for histology. It is an invasive test, requiring bowel preparation before the procedure but he is otherwise well and there are no contraindications in undertaking colonoscopy. Barium enema A barium enema, although it could be useful, is not the best test for this patient. It may give an impression of a lesion in the bowel wall but does not give such a ccurate information as would colonoscopy in this case. Furthermore he would still require an endoscopic biopsy if a lesion was seen. Capsule endoscopy Capsule endoscopy is an expensive test and not readily available. It is useful for looking for a source of gastrointestinal (GI) bleeding that occurs in the small bowel beyond the scope of the oesophago-gastroduodenoscopy (OGD) and proximal to the caecum/terminal ileum which cannot be accessed by colonoscopy. Computed tomography (CT) scan CT scans maybe usefu l for detecting gross bowel pathology and staging for cancers but would not be as useful as colonoscopy. Oesphagoduodenoscopy Oesphagoduodenoscopy (OGD) is useful if an upper gastrointestinal (GI) source is suspected but this patient has lower GI symptoms.

Answer 277

Explanation Melanosis coli Brownish discoloration on the wall of the sigmoid in a moiré pattern and characteristic pigment - laden macrophages within the mucosa with PAS staining on mucosal biopsy are characteristic features of melanosis coli and indicate la xative abuse. Although, colonoscopic appearance does not have any negative sequelae, chronic diarrhoea requires advice on stopping laxative abuse. Note her occupation as a model suggests she may feel pressurised to lose weight. Offer psychological support if required. Crohn’s disease Colonoscopic findings of Crohn’s disease include cobblestone appearance, in which oedematous islands of mucosa are separated by fissures. These can then extend through all layers of the bowel. Transmural involvement can lead to stricture and fistulae formation. Skip lesions are common where there is healthy bowel between diseased segments. Microscopically there can be deep fissuring ulcers, oedema and inflammatory cell infiltrates with foci of lymphocytes and non-caseating granulomas. Pigment -laden macrophages within the mucosa on PAS staining is not a feature of Crohn’s disease. Campylobacter infection Diagnosis of Campylobacter infection is made on direct microscopy of faeces or isolation of the organism. On sigmoidoscopy, the findings may be similar to those observed in pseudomembranous colitis or inflammatory bowel disease. These include mucosal oedema, hyperaemia, patchy petechiae and aphthoid ulceration. Pigment -laden macrophages within the mucosa on PAS staining is not a feature of Campylobacter infection. Diverticulitis Diverticulitis may present with similar features as mentioned in the history. In the current era of advanced imaging most of the complications of diverticulitis are diagnosed by computed tomography (CT) scan. However lower gastrointestinal (GI) endoscopy is required to rule out malignancy once the acute phase is over. Sigmoidoscopy may show openings of diverticulae. Pigment-laden macrophages within the mucosa on PAS staining is not a feature of diverticulitis . Ulcerative colitis On colonoscopy, inflammation is restricted to the mucosa and submucosa of the large bowel with ulcerative colitis. Abscesses develop at the base of the colonic crypts and once burst can lead to ulceration. Oedema of the intervening muc osa leads to pseudopolyp appearance. Histologically, there is chronic inflammatory cell infiltrate, crypt architectural distortion and goblet cell depletion. Granulomas are usually absent. Pigment -laden macrophages within the mucosa on PAS staining is not a feature of ulcerative colitis.

Answer 278

Explanation Ulcerative colitis This patient has ulcerative colitis as evident in history, endoscopy findings with confluent inflammation, and histology results. This inflammatory disorder differs from Crohn’s disease as granulomas are absent, fissures are rare and inflammation is superficial involving the mucosal layer. Crohn’s disease Colonoscopic findings of Crohn’s disease include a cobblestone appearance, in which oedematous islands of mucosa are separated by fissures. These can then extend through all layers of the bowel. Transmural involvement can lead to stricture and fistulae formation. Skip lesions are common where there is healthy bowel between diseased segments. Microscopically there can be deep fissuring ulcers, oedema and inflammatory cell infiltrates with foci of lymphocytes and non-caseating granulomas. Pigment -laden macrophages within the mucosa on periodic acid– Schiff (PAS) staining is not a feature of Crohn’s disease. Ischaemic colitis Ischaemic colitis presents in a similar way to inflammatory bowel disease or infectious colitis. Endoscopic findings that distinguish ischaemic colitis from inflammatory bowel disease are the segmental distribution, rectum sparing and rapid resolution on serial examinations. Histological changes in ischaemic colitis include oedema, distorted crypts, mucosal and submucosal haemorrhage, and inflammatory infiltration into the lamina propria, granulation tissue, intravascular platelet thrombi and necrosis. Diverticulitis Diverticulitis may present with similar features as mentioned in history. In the current era of advanced imaging most of the complications of diverticulosis are diagnosed by computed tomography (CT) scan. However lower gastrointestinal (GI) endoscopy is required to rule out malignancy once acute phase is over. Sigmoidoscopy may show openings of diverticulae. Salmonella infection Diagnosis of Salmonella infection is made clinically and with microbiological investigations. Colonoscopy may be required in some cases where complications such as bleeding occurs requiring endoscopic intervention. Colonoscopic findings include multiple variable -sized punched-out ulcers with slightly elevated margins. Moreover, the most commonly involved area is the terminal ileum, followed by the ileocecal valve and ascending/transverse colon. The left colon is usually spared.

Answer 279

Explanation Surgical resection of colonic lesion Definitive management of colovesical fistulae is surgical. It may be with curative or palliative intent depending upon the extent of local invasion. With curative intention it may include en bloc resection with or without pelvic exenteration. With palliative intent it may be urinary and faecal diversion leading to urostomy and colostomy respectively. Catheterisation This patient has developed a malignant colovesical fistula as a result of a sigmoid tumour. This patient will initially need a catheter but it is not the ‘definitive’ treatment requested. A fistula will not heal if there is distal obstruction – in this case an obstructing operative tumour. Neostigmine Neostigmine is an anticholinesterase agent that increases the effect of acetylcholine. It is helpful in the management of patients with neurogenic bladder having urinary retention. It is not helpful in patients having urinary retention due to a malignant colovesical fistula. Moreover, the question is regarding definitive management, which will be en bloc resection with or without pelvic exenteration; or faecal and urinary diversion in case of palliat ion. Stenting of the stricture Stenting may help in relieving colonic obstruction but it is not the definitive management of malignant colovesical fistulae. Neoadjuvant chemoradiotherapy In case of rectal tumour, neoadjuvant chemoradiotherapy reduces the r isk of recurrence. However, in the case of sigmoid tumours, neoadjuvant treatment is not recommended due to the high position of the tumour that can put the small bowel at risk of radiation enteritis.

Answer 280

Explanation Gastroschisis In gastroschisis there is no peritoneal covering, and it is rarely associated with congenital defects seen in patients with omphalocoele. However, sometimes it may be associated with intestinal atresia. Management initially consists of covering the defect with cling film to prevent heat and moisture loss, while establishing intravenous (IV) access for IV fluids. Umbilical hernia An umbilical hernia is covered by skin. The defect is herniation of the abdominal contents through the umbilical fibromuscular ring. Umbilical hernias usually occur in infants and reach their maximal size by the first month of life. Most hernias of this type close spontaneously by the first year of life, with only a 2–10% incidence in children older than 1 year. Omphalocoele major An omphalocoele is a congenital defect of the anterior abdominal wall in which the abdominal contents are covered by a sac. The sac has three layers: the perito neum, Wharton’s jelly, and the amnion. The sac may contain intestinal loops, the bladder, and the liver. Unlike gastroschisis it is often associated with other congenital anomalies. Contents in the case of omphalocoele protrude through the central defect in the abdomen and there is no umbilicus. Depending on the size of the defect it may be labelled as major or minor. A defect of more than 4 cm is designated major, while less than 4 cm it is minor. Hernia of the umbilical cord In a hernia of the umbilical cord a cuff of skin is seen extending from the abdominal wall onto the neck of the sac. The hernia sac comprises of the outer amnion and the inner peritoneal lining and contains contents varying from loops of bowel to any mobile intraperitoneal organs. Omphalocoele minor Omphalocoele minor is a congenital defect of the anterior abdominal wall in which the abdominal contents are covered by a sac and the defect is less than 4 cm.

Answer 281

Explanation Intussusception Intussusception is the commonest gastrointestinal surgical emergency in children between 3 months and 2 years. The ileocecal junction is the commonest location. A part of the bowel invaginates into the adjacent section, leading to obstruction. The patient usually presents with intermittent colicky abdominal pain lasting 1–2 min which frequently recurs. It is associated with vomiting. Blood is passed PR, often described as red-currant jelly in appearance. The invaginated bowel segment may be palpable as a sausage-shaped mass. Pyloric stenosis Presentation with vomit ing may mimic pyloric stenosis, however pyloric stenosis usually presents around the age of 4–6 weeks. Vomiting is projectile, bleeding per rectum is rare but an olive-shaped mass may be palpable in epigastric region. Diagnosis is by ultrasound (US) scan o f the abdomen. Electrolyte abnormalities include hypokalemia, hypochloraemic metabolic alkalosis with paradoxical aciduria. Treatment is by open or laparoscopic pyloromyotomy. Gastroenteritis The presentation may mimic acute gastroenteritis, however a palp able sausage-shaped mass is suggestive of intussusception. Midgut volvulus Midgut volvulus may present as a surgical emergency. With a 12 h history the abdomen is distended and tender and the child is usually in a state of shock. Such patients require emer gency laparotomy without any investigations. Necrotising enterocolitis Necrotising enterocolitis (NEC) is a condition that involves premature neonates. The usual presentation is greenish aspirates in a premature neonate who is in the Neonatal Intensive Car e Unit (NICU). The abdomen becomes shiny, tender and distended. An X -ray of the abdomen may show pneumatosis intestinalis. Treatment is medical (with antibiotics) or surgical depending upon the severity of the NEC.

Answer 282

Explanation Biliary atresia There are numerous causes of jaundice in neonates including physiological, med ical and surgical. Surgical causes include biliary atresia, choledochal cysts, spontaneous perforation of the bile duct, inspissated bowel within the common bile duct, and extrahepatic bile duct tumours. In biliary atresia the bile ducts are destroyed by inflammation. Clinical signs include jaundice, and the development of firm hepatosplenomegaly, pale stools and dark urine, which are not seen at birth. Children usually go to full term, but with a low birthweight. No single test is diagnostic of this condit ion. Choledochal cysts Choledochal cysts are congenital cystic dilatations of the biliary tree. Infants typically present with jaundice, pale stools and right upper quadrant mass. USS would classically reveal dilatation of the biliary tree. Extrahepatic bile duct tumour Bile duct tumours are uncommon and typically present with jaundice, affecting older patients with the average age of 60–65 years. Ileal atresia This is a malformation of the ileum resulting in a complete luminal obstruction and would typically be diagnosed within the first 24 h of birth if it had not been picked up on antenatal scans. The infant is unlikely to have passed stool, will have a distended abdomen and may be vomiting. Spontaneous perforation of the bile duct This is a rare conditio n affecting infants and children with the cause unknown. The infants can present acutely with biliary peritonitis or later with jaundice, pale stools and abdominal distension. An ultrasound would demonstrate ascites.

Answer 283

Explanation Small bowel atresia Small bowel atresia can be diagnosed antenatally. It presents with bilious vomiting, abdominal distension, and failure to pass further stools following passage of meconium. Plain abdominal X- ray shows distended loops of bowel with fluid levels. Duodenal atresia Duodenal atresia can be diagnosed antenatally. Abdominal distension is not marked as obstruction is proximal. In duodenal atresia a double gas bubble would be expected on abdominal X-ray. Hirschsprung’s disease In Hirschsprung’s disease there is failure in passage of meconium in the first 48 h in most cases. The rest of the findings may match with the above description. Rectal stimulation and washouts help in emptying the bowel unless the pathology involves whole of the colon. Meconium ileus In meconium ileus, passage of meconium fails to occur. X-ray findings may show a soap bubble appearance. Meconium ileus may be managed by rectal washouts in certain selected cases. Work up should include screening for cystic fibrosis. Oesophageal atresia With oesophageal atresia, excessive salivation and frothing occurs. A trial of passage of a nasogastric tube (NG) tube fails and X-rays show NG tube coiling in the oesophagus.

Answer 284

Explanation Pyloric stenosis Typical presentation is around 4–6 weeks in the first male baby of the family. Vomiting is projectile and non-bilious due to the high level of obstruction (the thickened pyloric muscle), which is above the entrance of the common bile duct into the duodenum. Distension is not usually a feature. Between the episodes the baby is eager to take feeds. Electrolyte disturbance s include hypokalaemic, and hypochloraemic metabolic alkalosis. Duodenal Atresia Vomiting is bilious and presentation is earlier following birth. Hirschprung’s disease Prominent features are inability to open the bowels and abdominal distension. Vomiting is a late feature and is bilious. Malrotation Presentation is with acute abdomen and bilious vomiting. If midgut volvulus has developed the baby requires emergency laparotomy. No further investigations should be done. Bilious vomiting in a newborn is a surgical emergency until proved otherwise. Malrotation is the diagnosis, which needs exclusion with an upper gastrointestinal (GI) contrast to look at the layout of the intestine, specifically whether the duodenal–jejunal flexure is on the correct side of the vertebrae – the left is the correct side. Meconium Ileus Presentation is at birth with abdominal distension, failure to pass stool and bilious aspirates.

Answer 285

According to the new Dukes’ staging it is B1 once the tumour has spread into the muscularis propria but has not penetrated through it. If it has penetrated through he propria, it is staged as B2. The original staging system derived by Cuthbert Dukes was:  A – Invasion into but not through the bowel wall (90% 5-year survival)  B – Invasion through the bowel wall but not involving lymph nodes (70% 5-year survival)  C – Involvement of lymph nodes (30% 5-year survival)  D – Distant metastases. This was revised by Astler–Coller in 1954:  A – Limited to mucosa  B1 – Into muscularis propria but not penetrating it. No nodes.  B2 – Penetrating muscularis propria. No nodes.  C1 – Metastasis to one to four regional lymph nodes  C2 – Metastasis to more than four lymph nodes.  D – Distant metastases. Dukes' A If the tumour is limited to the mucosa it is classified as Dukes’ A. Dukes' C1 If the tumour has spread into regional lymph nodes (between one and four) it is staged as C1. Dukes' C2 Spread to lymph nodes beyond the regional lymph nodes (more than four) is classified as C2. Dukes' D Distant metastasis is classified as stage D.

Answer 286

Explanation Adenocarcinoma of the intestinal type The lower end of the oesophagus is prone to develop metaplastic changes in response to reflux oesophagitis. Change of normal squamous epithelium to columnar type is called as Barrett’s oesophagus. These changes are reversible. However, in longst anding cases, dysplasia may occur that can lead to adenocarcinoma. As the mass in the summary is in the lower oesophagus then, most probably, malignant adenocarcinoma is the most likely diagnosis. Squamous cell carcinoma Squamous cell carcinoma occurs in t he upper part of the oesophagus. Malignant melanoma Primary and metastatic malignant melanoma may occur in some patients, but it is a very rare problem. Moreover history and endoscopic findings are more suggestive of adenocarcinoma. Metaplastic columnar epithelium This is suggestive of Barrett’s oesophagus. Oesophageal squamous epithelium is replaced by columnar epithelium of the intestinal type with goblet cells. Adenocarcinoma may develop in longstanding cases of Barrett’s oesophagus. Dysplastic columnar epithelium This finding is suggestive of dysplasia in Barrett’s oesophagus. It is a premalignant condition and can lead to adenocarcinoma of the lower end of the oesophagus and longstanding cases of gastro-oesophageal reflux disease (GORD). Oesophageal carcinoma is divided into an adenocarcinoma, which affects the distal one-third (50–80%) and squamous cell carcinomas (90– 95%), which affect the upper two -thirds. Squamous cell carcinomas are associated with tobacco (as is adenocarcinoma) and also alcohol intake, whereas adenocarcinoma is closely linked to GORD and Barrett’s oesophagus. Most oesophageal cancers present late and therefore are not suitable for minimally invasive surgery. Sadly, palliation is often the only treatment available.

Answer 287

Explanation Linitis plastica Gastric linitis plastica is a diffuse type of cancer. Malignant cells invade throughout the stomach, resulting in the thickening and rigidity of the stomach wall. Most of the patients present late. Endoscopically the stomach looks thick with reduced distensibility. Biopsy reveals invasion of all the layers of the stomach in a diffuse pattern. Malignant cells look like a signet ring. Prognosis is poor and treatment may include radical surgery or palliative chemotherapy. Metastatic tumours of the stomach These tumours may present as ulcers or diffused stomach thickening, however biopsy will reveal the site of origin of such metastasis. Gastrointestinal stromal tumour (GIST) Small gastric GISTs appear as serosal, submucosal or intramural nodules. They are usually incidental findings during abdominal surgery or endoscopy. Histologically these are positive for KIT tyrosine kinase receptors. Gastric carcinoid Histology shows enterochromaffin like (ECL) cells that are a distinctive type of neuroendocrine cell in the gastric mucosa underlying the epithelium. Gastric Lymphoma Gastric lymphomas may be primary or secondary. Endoscopically, these are visible as enlarged gastric folds, or ulcers in the case of low grade lesions and a mass in the case of high grade lesions. Histology and immunohistochemistry may differentiate between different types of lymphomas.

Answer 288

Explanation There is a strong association between heavy alcohol intake and stomach cancer There is significant body of evidence suggesting that a heavy alcohol intake increases gastric cancer risk. Smoking also increases the risk from 40% increased risk for current smokers to 82% increased risk for heavy smokers. Other risk factors include autoimmune atrophic gastritis, pernicious anaemia, Menetrier disease and intestinal metaplasia. The majority of H.pylori infections result in stomach cancer H. pylori infection is the main risk factor for 65–80% of gastric carcinomas but these only occur in approximately 2% of infections. Gastric carcinoma is commoner in women than men Men are affected more co mmonly than women. Linitis plastica tends to be associated with H.pylori infection Linitis plastica tends not to be associated with H. pylori and has a more genetic association. Gastrointestinal stromal tumours form the most common histological subtype of gastric cancer The most common subtype of gastric cancer is adenocarcinoma (90 –95%). Other histological subtypes include: lymphoma (1–5%), gastrointestinal stromal tumours (2%), carcinoids (1%), adenoacanthomas (1%) and squamous cell carcinoma (1%).

Answer 289

Explanation It is characterised by polyps typically present in the small bowel Polyps in Peutz–Jeghers are typically present in the small bowel but may affect the entire gastrointestinal (GI) tract. It is an autosomal-recessive condition Peutz–Jeghers is an autosomal-dominant condition. It is associated with germ-line mutations in the STK11 gene on chromosome 19. Pigmentation is limited to the circumoral skin and buccal mucosa Pigmentation can also affect the hands and genitalia. Histological examination of polyps adenomas Polyps in Peutz–Jeghers in are hamartomas. There is no increased risk of cancer with this condition Hamartomas are usually benign; there is a very small risk of malignant transformation. However, there is also an increased risk of pancreatic, breast, lung, ovarian and endometrial cancer associated with Peutz–Jeghers syndrome.

Answer 290

Explanation It is mainly associated with hepatitis B and C viruses Hepatitis B virus (HBV) and hepatitis C virus (HCV) are well known causes of HCC. HBV is a major independent risk factor and, in countries where it is prevalent, 90% of patients with HCC are positive for HBV. With HCV the HCC classically develops in the setting of cirrhosis. Women are affected more than men Men are more commonly affected than women (3:1). It is associated with type 1 diabetes Although not completely understood there is an increased risk of HCC in type 2 diabetes and relates to poor glucose control and insulin levels. Serum a-fetoprotein is normal Serum α-fetoprotein is a tumour marker and is usually raised in HCC. It is also raised in other cancers such as testicular and ovarian tumours. Usually presents below the age of 30 HCC usually presents later with the average age at diagnosis of 65 years.

Answer 291

Explanation It is 60 cm from the ileocaecal valve It is classically found in the distal ileum, 60 cm (2 feet) from the ileocaecal valve on the antimesenteric border of the ileum and is approximately 5 cm (2 inches) long. It involves two layers of the intestinal wall only A Meckel’s diverticulum is an example of a true diverticulum and contains all the layers of the intestinal wall. It is seen in 2% of people, usually presenting in patients over two years of a ge While it is present in 2% of people, most symptomatic cases will present before the age of 2. It is usually found in the jejunum on the antimesenteric border and is approximately 5 cm long It is classically found in the distal ileum, 60 cm from the ileo caecal valve on the antimesenteric border and is approximately 5 cm long. It occurs twice as frequently in women than in men Meckel’s diverticulum occurs in 2% of the population and affects men twice as often as women.

Answer 292

Explanation It is associated with Edward syndrome Associated syndromes include Beckwith–Wiedemann syndrome (features include macroglossia, macrosomia, omphalocele/exomphalos, umbilical hernia, ear pits, neonatal hypoglycaemia, hepatoblastoma), Edward syndrome (trisomy 18, features include heart defects, omphalocele, oesophageal atresia, microcephaly, micrognathia, cleft lip/palate, widely spaced eyes, ptosis, webbing of toes, undescended testicles) and Patau syndrome (trisomy 13, features include microcephaly, structural eye defects, polydactyly, low-set ears, omphalocele, rocker-bottom feet, abnormal genitalia and heart defects). In the vast majority of cases in which exomphalos is present it is the only congenital abnormality The incidence of associated abnormalities is between 40–70%, including chromosomal (trisomies 13, 18 and 21), cardiac, genitourinary, gastrointestinal, craniofacial, and pulmonary hypoplasia. Maternal smoking decreases the risk of developing it Both maternal alcohol use and heavy smoking are associated with an increased ris k. Its incidence is decreasing Incidence is 1 in 5000 to 1 in 10 000 live births although the incidence seems to be increasing worldwide. It is associated with Potter syndrome Potter syndrome or sequence relates to renal abnormalities, it is not associated with exomphalos. Oligohydramnios as a result of renal abnormalities, urinary tract obstruction or amniotic fluid leakage may lead to fetal compression with joint contractures (arthrogryposis), pulmonary hypoplasia and squashed facies.

Answer 293

Explanation 50% Calot’s triangle, also known as the cystohepatic or hepatobiliary triangle is an anatomic space that is of great relevance when performing a laparoscopic cholecystectomy. It is bounded by the common hepatic duct medially, cystic duct laterally and liver superiorly, and is used to locate the cystic artery which runs within. Anomalies of the gall-bladder or biliary tree are found within 50% of subjects and are important during surgery. There are a vast array of different anomalies that can occur, by way of example these anomalies include:  Anomalous ducts in around 12% – around 85% of which are found (and occasionally injured) within Calot’s triangle.  Anomalous gall-bladder development – rarely agenesis of the gall-bladder (around 0.02%), more commonly multiple gall bladders around (1 in 3800), or other anomalies such as the gall-bladder opening directly into the side of the common bile duct ie the cystic duct is absent.  Variation in the blood vessel arrangement supplying the gall-bladder eg in 25% of people the right hepatic artery crosses in front of the common hepatic duct instead of behind it. <1% Difficult biliary anatomy is relatively common, often making what is usually a routine operation very difficult. 25% This answer is not correct, the correct answer is 50%. 75% The variant anatomy encountered is less than this percentage. >90% This estimate is not correct.

Answer 294

Explanation Paediatric biliary atresia Biliary atresia is of unknown aetiology. The extra-hepatic bile ducts are destroyed by inflammation. It present s with jaundice, pale stools and dark urine with hepatosplenomegaly. An absent gall bladder is characteristic finding of extrahepatic biliary atresia as it is atretic. Treatment requires a Kasai’s procedure, this involves removal of all the extrahepatic tr ee and portoenterostomy. Outcome is poor if diagnosis is delayed. Breast milk jaundice Breast milk jaundice is a type of neonatal jaundice that is associated with breastfeeding. It is characterized by indirect hyperbilirubinemia in an otherwise healthy breastfed neonate. Signs of obstructive jaundice mentioned in the summary will be absent. Diagnosis is by exclusion. Hepatocellular cholestasis Hepatocellular cholestasis results from stasis of bile pigments within the liver. The underlying aetiology can include any of viral hepatitis, Alpha1-antitrypsin deficiency, inborn errors of bile acid synthesis, drug-induced cholestasis or total parenteral nutrition (TPN) associated cholestasis. However, the clinical and biochemical picture differs as features of obstructive jaundice will be absent. Haemolytic disease of the new-born The jaundice is of non-obstructive variety. It results from rhesus incompatibility. Antibodies against Rh +ve red blood cells cross the placenta and cause haemolysis. Depending upon seve rity the disease may range from hydrops fetalis to neonatal jaundice at birth. Laboratory investigations may show indirect hyperbilirubinemia. Choledochal cyst The presentation closely resembles that of extrahepatic biliary atresia. The differentiating poi nt is presence of a gall-bladder. A choledochal cyst on ultrasound may also be visible.

Answer 295

Explanation Decreased parathyroid hormone (PTH) The terminal ileum is an important site of bile salt re-absorption, excess loss of bile salts which are responsible solubilising lipids in the jejunum. The excess loss of bile salts therefore leads to fat malabsorption and excess fatty acids within the distal bowel – these can chelate magnesium causing hypomagnesaemia (not hyper). Hypomagnesaemia has a suppressive effect on parathyroid hormone (PTH) release resulting in acquired hypoparathyroidism. A microcytic anaemia The terminal ileum is the site of vitamin B 12 absorption – malabsorption leads to development of a macrocytic anaemia. Hyperparathyroidism The terminal ileum is an important site of bile salt re-absorption. Excess loss of bile salts, which are responsible solubilising lipids in the jejunum, can occur. The excess loss of bile salts leads to fat malabsorption and excess fatty acids within the distal bowel – these fatty acids can chelate magnesium causing hypomagnesaemia (not hypermagnesaemia). Hypomagnesaemia has a suppressive effect on parathyroid hormone (PTH) release resulting in acquired hypoparathyroidism. Vitamin K excess The terminal ileum is an important site of bile salt re-absorption, and therefo re loss results in fat and fat soluble vitamin (vitamins A, D, E and K) malabsorption. Hypermagnesaemia The terminal ileum is an important site of vitamin B 12 absorption as well as bile salt re- absorption. Loss of bile salts results in fat malabsorption and excess fatty acids within the distal bowel – these can chelate magnesium. This leads to hypomagnesaemia (not hypermagnesaemia).

Answer 296

The correct answer is C1. Explanation: The modified Astler–Coller staging system for colorectal cancer is as follows: • Stage A: Limited to the mucosa. • Stage B1: Extending into the muscularis propria but not penetrating through it; no lymph node involvement. • Stage B2: Penetrating through the muscularis propria; no lymph node involvement. • Stage C1: Extending into the muscularis propria but not penetrating through it; lymph nodes involved. • Stage C2: Penetrating through the muscularis propria; lymph nodes involved. • Stage D: Distant metastatic spread. Since the histology report indicates that the tumour extends into but not through the muscularis propria and involves a local lymph node, it corresponds to Stage C1 .

Answer 297

The muscle affected due to injury to the long thoracic nerve is the serratus anterior. The long thoracic nerve innervates the serratus anterior muscle. Injury to this nerve can lead to a condition known as “winged scapula,” where the shoulder blade protrudes out abnormally. This can occur during surgeries such as a radical mastectomy, where the nerve may be damaged accidentally. The serratus anterior muscle plays a crucial role in the movement and stabilization of the scapula, particularly in protraction and upward rotation. So, the correct answer is: C. Serratus anterior

Answer 298

The roots of the fifth and sixth cervical nerves contribute significantly to the brachial plexus, particularly forming the upper trunk, which eventually gives rise to several nerves that innervate specific areas of the upper limb. When these nerve roots are torn, it typically affects the areas supplied by the nerves that arise from these roots. In this scenario, the cutaneous areas most affected would be those innervated by the C5 and C6 dermatomes. These areas include: • The top of the shoulder (innervated by the supraclavicular nerves, which are derived from C3 and C4 but can be affected indirectly due to proximity). • The lateral side of the arm (innervated by the axillary nerve from C5 and C6). • The lateral aspect of the forearm (innervated by the musculocutaneous nerve, which has contributions from C5, C6, and C7). Given this information, the part of the upper limb that will have diminished cutaneous sensations in this patient is: B. The top of the shoulder and the lateral side of the arm

Answer 299

The muscle most likely to be affected by an olecranon fracture is the triceps brachii, as the tendon of the triceps inserts on the olecranon process of the ulna. An olecranon fracture can disrupt the triceps’ ability to extend the elbow. So, the correct answer is: E. Triceps brachii

Answer 300

Extension of the humerus is primarily facilitated by muscles such as the latissimus dorsi and the long head of the triceps brachii. Among the nerves listed, the one that innervates the latissimus dorsi is the thoracodorsal nerve. An injury to the thoracodorsal nerve would impair the function of the latissimus dorsi muscle, leading to a limitation in the extension of the humerus. Therefore, the correct answer is: D. Thoracodorsal nerve

Answer 301

The annular ligament is an important structure in the elbow joint. It specifically stabilizes the proximal radioulnar joint by holding the head of the radius in place as it articulates with the ulna. The correct description of the annular ligament is: A. Encircles the head of the radius

Answer 302

The brachial artery provides several branches that contribute to the anastomotic circulation around the elbow joint, ensuring adequate blood supply to the area despite movements that might otherwise impede blood flow. Therefore, the correct answer is: B. Elbow joint

Answer 303

The supraspinatus muscle is primarily responsible for initiating the first 15 degrees of abduction of the humerus at the shoulder joint. Injury to this muscle would specifically impair this initial movement, though full abduction can still be carried out by the deltoid muscle after the first 15 degrees. Therefore, the correct answer is: D. Initiation of abduction of the humerus

Answer 304

The lateral thoracic artery is a branch of the axillary artery, specifically from its second part. This artery accompanies the long thoracic nerve and supplies blood to the serratus anterior muscle, among other structures. Therefore, the correct answer is: C. Accompanies the long thoracic nerve to the serratus anterior muscle

Answer 305

The muscle that acts to depress the glenoid fossa directly is the pectoralis minor. This muscle attaches to the coracoid process of the scapula and, when contracted, it pulls the scapula forward and downward, which in turn depresses the glenoid fossa. Therefore, the correct answer is: A. Pectoralis minor

Answer 306

The common flexor tendon of the forearm is the origin for several muscles located in the superficial and intermediate layers of the anterior (flexor) compartment of the forearm. One of the primary muscles that originates from this tendon is the flexor digitorum superficialis. Therefore, the correct answer is: A. Flexor digitorum superficialis

Answer 307

The correct answer is D) Extensor carpi radialis brevis and extensor carpi ulnaris. The abduction of the wrist is the movement of the hand away from the midline of the body. This motion is primarily accomplished by the combined action of two muscles: 1. Extensor carpi radialis brevis: This muscle originates from the lateral epicondyle of the humerus and inserts into the base of the third metacarpal bone. When contracted, it extends and abducts the wrist. 2. Extensor carpi ulnaris: This muscle originates from the lateral epicondyle of the humerus and inserts into the base of the fifth metacarpal bone. When contracted, it extends and abducts the wrist. The other muscle combinations mentioned in the options are involved in different movements of the wrist and forearm: A) Pronator teres and brachioradialis are involved in pronation and flexion of the forearm, respectively. B) Palmaris longus and extensor digitorum are involved in flexion of the wrist and extension of the digits, respectively. C) Extensor carpi radialis brevis and flexor carpi radialis are involved in abduction and flexion of the wrist, respectively. E) Supinator and extensor pollicis longus are involved in supination of the forearm and extension of the thumb, respectively. Therefore, the correct combination of muscles responsible for abducting the wrist is extensor carpi radialis brevis and extensor carpi ulnaris.

Answer 308

The correct statement regarding adduction of the digits of the hand is D) All of the adductors of the digits take at least part of their attachments from metacarpal bones. Explanation: A) Incorrect. The palmar interossei are not the sole adductors of the digits. The lumbrical muscles and the adductor pollicis also contribute to adduction. B) Correct. The lumbrical muscles are responsible for adduction of the fingers at the metacarpophalangeal joints. C) Incorrect. There is only one muscle specifically responsible for adduction of the thumb, which is the adductor pollicis. D) Correct. All of the muscles responsible for adduction of the digits take at least part of their attachments from the metacarpal bones. The lumbrical muscles originate from the tendons of the flexor digitorum profundus and insert onto the radial side of the proximal phalanges and extensor expansions. The palmar interossei originate from the sides of the metacarpal bones and insert onto the bases of the proximal phalanges and extensor expansions. The adductor pollicis originates from the capitate bone and the bases of the 2nd and 3rd metacarpals and inserts onto the base of the proximal phalanx of the thumb. E) Incorrect. Carpal tunnel syndrome primarily affects the median nerve, which does not directly innervate the muscles responsible for adduction of the digits. Carpal tunnel syndrome can affect the thenar and hypothenar muscle groups, which are responsible for abduction and opposition of the thumb and little finger, respectively. Therefore, the correct statement is D) All of the adductors of the digits take at least part of their attachments from metacarpal bones.

Answer 309

The correct answer is A) Ulnar nerve. The ulnar nerve innervates the intrinsic muscles of the hand, which are responsible for various movements, including adduction of the digits. When the ulnar nerve is damaged, as in the case of a severed nerve in the right upper limb, it can result in the loss of adduction of the digits of the affected hand. This condition is known as ulnar nerve palsy. Source: • Nerve injuries of the hand: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982572/

Answer 310

The correct answer is D) Lateral pectoral nerve. The lateral cord of the brachial plexus gives rise to several nerves, one of which is the lateral pectoral nerve. This nerve innervates the pectoralis major muscle, assisting in its function. Source: • Brachial Plexus Anatomy: https://teachmeanatomy.info/upper-limb/nerves/brachial-plexus/

Answer 311

A rugby player who sustained a spinal cord injury at the C8 level is likely to experience specific neurological deficits based on the functions innervated by the C8 nerve roots. Here is an analysis of the options provided: ### A. The brachialis muscle will be paralysed - The brachialis muscle is primarily innervated by the musculocutaneous nerve, which originates from the C5 and C6 nerve roots. Therefore, a C8 spinal cord injury would not typically affect the brachialis muscle. ### B. The muscles innervated by the radial nerve that would most likely be affected would be the most proximal ones - The radial nerve innervates muscles in the posterior compartment of the arm and forearm, including the triceps brachii and the extensor muscles of the forearm. Since the radial nerve receives contributions from C5 to T1, a C8 injury would not selectively affect the most proximal muscles but could impact the muscles innervated by the C8 and T1 roots, which are more distal. ### C. The hypothenar muscles would be completely paralysed - The hypothenar muscles are innervated by the ulnar nerve, which receives fibers from the C8 and T1 nerve roots. A C8 spinal cord injury could indeed affect the hypothenar muscles, potentially leading to paralysis or significant weakness in these muscles[4][6]. ### D. Innervation to the deltoid muscle would be affected - The deltoid muscle is innervated by the axillary nerve, which originates from the C5 and C6 nerve roots. Therefore, a C8 spinal cord injury would not affect the innervation to the deltoid muscle[3][5]. ### E. The patient would be unable to flex their humerus - Flexion of the humerus at the shoulder joint involves muscles such as the deltoid (anterior fibers) and the pectoralis major, which are innervated by nerves originating from the C5 and C6 nerve roots. Thus, a C8 spinal cord injury would not typically impair the ability to flex the humerus[5]. ### Conclusion The most likely outcome for a patient with a C8 spinal cord injury is that the hypothenar muscles would be completely or significantly paralyzed due to the involvement of the ulnar nerve, which is innervated by the C8 and T1 nerve roots. Therefore, the correct answer is: **C. The hypothenar muscles would be completely paralysed**

Answer 312

The intertubercular groove of the humerus, also known as the bicipital groove, contains the tendon of the long head of the biceps brachii muscle. This groove is a deep indentation on the humerus that separates the greater tubercle from the lesser tubercle and allows for the passage of the long tendon of the biceps brachii muscle, which is enveloped in a synovial sheath[2][3][4][6]. Therefore, the correct answer is: **E. Tendon of the long head of the biceps brachii muscle** Sources [1] Radiographic anatomy of the intertubercular groove of the humerus https://pubmed.ncbi.nlm.nih.gov/3996427/ [2] Intertubercular sulcus - AnatomyZone https://anatomyzone.com/articles/intertubercular-sulcus/ [3] Bicipital groove - Wikipedia https://en.wikipedia.org/wiki/Bicipital_groove [4] The Humerus - Proximal - Shaft - Distal - TeachMeAnatomy https://teachmeanatomy.info/upper-limb/bones/humerus/ [5] Intertubercular Tendon Sheath | Complete Anatomy - Elsevier https://www.elsevier.com/resources/anatomy/connective-tissue/connective-tissue-of-upper-limb/intertubercular-tendon-sheath/21848 [6] Review of Bicipital Groove Morphology and Its Analysis in North ... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392950/ [7] Intertubercular Sulcus | Complete Anatomy - Elsevier https://www.elsevier.com/resources/anatomy/skeletal-system/appendicular-skeleton/intertubercular-sulcus/24211 [8] Humerus: Anatomy and clinical notes - Kenhub https://www.kenhub.com/en/library/anatomy/the-humerus

Answer 313

Based on the information provided in the search results, the correct answer is C) Brachial artery. The key evidence comes from the following excerpts: "The superior ulnar collateral artery is a vessel arising from the brachial artery at the middle part of the arm." [2] "The superior ulnar collateral artery arises from the brachial artery." [3] "The superior ulnar collateral artery (inferior profunda artery), of small size, arises from the brachial artery a little below the middle of the arm." Multiple authoritative sources clearly state that the superior ulnar collateral artery originates as a branch from the brachial artery in the middle/upper arm region. Therefore, the brachial artery is the direct parent vessel that gives rise to the superior ulnar collateral artery. [2][3] Sources [1] Superior ulnar collateral artery | Radiology Reference Article https://radiopaedia.org/articles/superior-ulnar-collateral-artery?lang=gb [2] Superior Ulnar Collateral Artery | Complete Anatomy - Elsevier https://www.elsevier.com/resources/anatomy/cardiovascular-system/arteries/superior-ulnar-collateral-artery/19414 [3] Superior ulnar collateral artery - Wikipedia https://en.wikipedia.org/wiki/Superior_ulnar_collateral_artery [4] Superior Ulnar Collateral Artery Anatomy, Function & Diagram https://www.healthline.com/human-body-maps/superior-ulnar-collateral-artery/male [5] Inferior ulnar collateral artery - Wikipedia https://en.wikipedia.org/wiki/Inferior_ulnar_collateral_artery [6] Anterior ulnar recurrent artery - Wikipedia https://en.wikipedia.org/wiki/Anterior_ulnar_recurrent_artery [7] Ulnar artery: Branches, definition, clinical notes - Kenhub https://www.kenhub.com/en/library/anatomy/the-ulnar-artery [8] Posterior ulnar recurrent artery - Wikipedia https://en.wikipedia.org/wiki/Posterior_ulnar_recurrent_artery [9] Brachial artery: Anatomy and branches - Kenhub https://www.kenhub.com/en/library/anatomy/brachial-artery [10] Medial collateral artery - Wikipedia https://en.wikipedia.org/wiki/Medial_collateral_artery [11] Radial collateral artery - Wikipedia https://en.wikipedia.org/wiki/Radial_collateral_artery [12] Brachial artery - Wikipedia https://en.wikipedia.org/wiki/Brachial_artery [13] Anatomy, Shoulder and Upper Limb, Profunda Brachii Artery - NCBI https://www.ncbi.nlm.nih.gov/books/NBK542225/ [14] Ulnar nerve - Wikipedia https://en.wikipedia.org/wiki/Ulnar_nerve [15] Brachial artery | Radiology Reference Article | Radiopaedia.org https://radiopaedia.org/articles/brachial-artery?lang=gb [16] Superior ulnar collateral artery - e-Anatomy - IMAIOS https://www.imaios.com/en/e-anatomy/anatomical-structure/superior-ulnar-collateral-artery-1553673144 [17] Posterior ulnar recurrent artery | Radiology Reference Article https://radiopaedia.org/articles/posterior-ulnar-recurrent-artery?lang=gb

Answer 314

The correct answer is D) Form the trunks of the brachial plexus. The key evidence from the search results: [2] "The brachial plexus consists of roots, trunks, divisions, cords and terminal branches as it travels from proximal to distal upper limb...Roots are formed between the scalenus anterior and scalenus medius muscles by the anterior rami of C5-C8 and T1 nerve roots...Trunks form from the roots as they pass between scalenus anterior and medius muscles." [3] "The ventral rami of C5 to T1 are referred to as the "roots" of the plexus...Shortly after emerging from the intervertebral foramina, the 5 roots (C5-T1) unite to form 3 trunks." [4] "The brachial plexus is formed by the anterior rami (divisions) of cervical spinal nerves C5, C6, C7 and C8, and the first thoracic spinal nerve, T1...The 'roots' refer the anterior rami of the spinal nerves that comprise the brachial plexus." [5] "The brachial plexus is formed by the anterior primary rami of C5 through T1...The 3 trunks continue from the posterior triangle into the axilla, with C5 and C6 roots forming the superior trunk, C8 and T1 roots forming the inferior trunk, and the C7 root continuing as the middle trunk." Multiple authoritative sources clearly state that the ventral/anterior rami of the spinal nerves C5-T1 form the roots of the brachial plexus, and these roots then combine to form the three trunks (superior, middle, inferior) of the brachial plexus. Therefore, the primary ventral rami directly give rise to and form the trunks of the brachial plexus. [2][3][4][5] Sources [1] Anatomy of the Ventral Rami, Upper Trunk, and Its Divisions and ... https://www.sciencedirect.com/science/article/abs/pii/B9780124103900000408 [2] Brachial plexus | Radiology Reference Article | Radiopaedia.org https://radiopaedia.org/articles/brachial-plexus?lang=gb [3] Overview, Gross Anatomy, Blood Supply of the Brachial Plexus https://emedicine.medscape.com/article/1877731-overview [4] The Brachial Plexus - Sections - Branches - TeachMeAnatomy https://teachmeanatomy.info/upper-limb/nerves/brachial-plexus/ [5] Anatomy, Head and Neck: Brachial Plexus - StatPearls - NCBI https://www.ncbi.nlm.nih.gov/books/NBK531473/

Answer 315

Based on the information provided in the search results, the correct answer is B) Pronator teres. The key evidence comes from the following excerpts: [1] "The muscles that act on the proximal radioulnar joint to produce pronation are pronator quadratus and pronator teres. The force of the pronator teres is included in fast movements and movements against resistance." [2] "Pronation: Produced by the pronator quadratus and pronator teres." [3] "Rotatory movements of the head of the radius within the collar formed by the annular ligament and the radial notch, allowing...pronation (by the action of pronator teres and pronator quadratus muscles)." Multiple authoritative sources clearly state that the pronator teres muscle is one of the primary muscles responsible for producing the pronation movement at the proximal radioulnar joint. The pronator teres is specifically mentioned as being involved in faster, more forceful pronation movements. Therefore, if the muscle producing the main pronation movement at the proximal radioulnar joint was paralyzed following a stab wound to the cubital fossa (where the pronator teres passes through), the paralyzed muscle would be the pronator teres. [1][2][3] Sources [1] Proximal radioulnar joint: Anatomy, movements - Kenhub https://www.kenhub.com/en/library/anatomy/proximal-radioulnar-joint [2] The Radioulnar Joints - TeachMeAnatomy https://teachmeanatomy.info/upper-limb/joints/radioulnar-joints/ [3] Proximal radioulnar joint | Radiology Reference Article - Radiopaedia https://radiopaedia.org/articles/proximal-radioulnar-joint-2?lang=gb [4] elbow and radio-ulnar joints https://ouhsc.edu/bserdac/dthompso/web/namics/elbow.htm [5] Elbow joint: Anatomy, ligaments, movements, blood supply | Kenhub https://www.kenhub.com/en/library/anatomy/elbow-joint

Answer 316

E) It prevents the tendons of the posterior compartment of the forearm from 'bowstringing' when the hand is extended at the wrist. This statement is correct based on the information provided in the search results: [1] "The extensor retinaculum of the wrist holds the extensor tendons in position and prevents bowstringing of the tendons." [2] "Extensor Retinaculum helps to keep the extensor tendons in alignment and prevent bowstringing during movements." [3] "The extensor retinaculum is a thickened portion of the antebrachial fascia that holds the tendons of the extensor muscles in place...It is located on the back of the forearm, just proximal to the hand." [4] "The extensor retinaculum of the wrist is the broad ligamentous sheet located at the dorsal aspect of the wrist and functions to keep the extensor tendons in alignment and prevent bowstringing during movement." Multiple authoritative sources clearly state that the main function of the extensor retinaculum is to prevent the extensor tendons passing through the posterior compartment of the forearm from bowstringing or deviating away from the wrist when the hand is extended. [1][2][3][4] The other options are incorrect based on the information given: A) It is not an extension of the axillary fascia, but rather the antebrachial fascia. B) The median nerve does not run deep to the extensor retinaculum. C) The brachioradialis tendon does not pass through the extensor retinaculum compartments. D) It does not contain a compartment for the thenar (intrinsic hand) muscles. Sources [1] Extensor Retinaculum of Wrist | Complete Anatomy - Elsevier https://www.elsevier.com/resources/anatomy/connective-tissue/fasciae/extensor-retinaculum-of-wrist/17913 [2] Extensor Retinaculum (Wrist) - Physiopedia https://www.physio-pedia.com/Extensor_Retinaculum_%28Wrist%29 [3] Extensor retinaculum of the hand - Wikipedia https://en.wikipedia.org/wiki/Extensor_retinaculum_of_the_hand [4] Extensor retinaculum (wrist) | Radiology Reference Article https://radiopaedia.org/articles/extensor-retinaculum-wrist?lang=gb [5] The extensor retinaculum of the wrist - PubMed https://pubmed.ncbi.nlm.nih.gov/6747233/

Answer 317

Correct Answer: 3. Intravenous fluids and anticoagulation Explanation: Severe ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation characterized by enlarged ovaries, fluid accumulation in the abdomen (ascites), and a risk of thromboembolism due to hemoconcentration. Management includes supportive care with intravenous fluids to maintain intravascular volume, anticoagulation to prevent thromboembolic events, and careful monitoring. Immediate laparotomy and high-dose corticosteroids are not indicated. Oral contraceptive pills are not useful in the acute management of OHSS. Watchful waiting is inappropriate due to the severity of the symptoms and the potential for rapid deterioration. Explanation It is important to ascribe a severity to cases of OHSS for audit purposes, and a classification of mild, moderate, severe or critical exists. Features of severe OHSS include: Clinical ascites (± hydrothorax) Oliguria (< 300 ml/day or < 30 ml/hour) Haematocrit > 0.45 Hyponatraemia (sodium < 135 mmol/l) Hypo-osmolality (osmolality < 282 mOsm/kg) Hyperkalaemia (potassium > 5 mmol/l) Hypoproteinaemia (serum albumin < 35 g/l) Ovarian size usually > 12 cma Reference: Royal College of Obstetricians and Gynaecologists (RCOG) Ovarian Hyperstimulation Syndrome, Management (Green-top Guideline No. 5).

PASTEST Flashcards

(341 cards)