Histopathology SBAs+EMQs Flashcards
A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 36-year-old man presents to accident and emergency with a 1-day history of a fever of 39.2°C and night sweats. A new heart murmur is detected by the oncall cardiologist. The patient admits to being an intravenous drug user.
B Infective endocarditis Infective endocarditis (IE; B) results from bacterial-vegetation of heart valves. Acute IE has a time course of days and is usually caused by Staphylococcus aureus in intravenous drug users; both sides of the heart can be affected, but the right heart is most commonly affected, because the lungs filter out many organisms, so that the left side of the heart gets less exposure to organisms. Subacute IE has a time course of weeks/months and is generally secondary to Streptococcus viridans infection after dental procedures; only abnormal valves are affected and hence these are more likely to be on the left side of the heart because those valves are more commonly damaged as they are on the high pressure side of the heart. Perforation of the valve leaflets and rupture of papillary muscles may lead to aortic or mitral regurgitation.
A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 64-year-old man presents to accident and emergency due to a collapse at home. An ejection systolic murmur is heard at the upper-left sternal edge.
H Aortic stenosis Aortic stenosis (H) occurs when there is an opening defect in the aortic valve. Causes include age-related degenerative calcification, rheumatic heart disease and congenital malformations (bicuspid valve). Calcification is confined to the cusps. Clinical presentation includes syncope, angina and dyspnoea. On examination an ejection systolic murmur, narrow pulse pressure and/or slow rising pulse may be detected. If due to a bicuspid valve an ejection systolic click may be heard. Left ventricular hypertrophy may develop as a consequence of chronic pressure overload.
A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A widowed 72-year-old woman who has passed away at home is sent for autopsy due to unknown cause of death. Post-mortem examination reveals a nutmeg liver and haemosiderin-laden macrophages in the lungs.
F Left heart failure Left heart failure (F) results in the inability of the heart to meet the demands of the body. It is either due to increased demand (high output failure) or reduced supply (low output failure) of blood. Causes of high output failure include severe anaemia and hyperthyroidism, while low output failure occurs due to ischaemic heart disease, hypertension and aortic/mitral valve defects. Clinical features include dyspnoea, orthopnoea and paroxysmal nocturnal dyspnoea. Histological findings include dilated ventricles, thin walls, nutmeg liver and haemosiderin macrophages in the lungs.
A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 54-year-old man presents to accident and emergency with fever and pleuritic chest pain. It is noted that the patient suffered a myocardial infarction 4 weeks previously.
C Dressler’s syndrome Dressler’s syndrome (C) is an autoimmune complication of myocardial infarction (MI) that occurs approximately 4 weeks after the episode. It is characterized by chest pain, fever and a pericardial rub. The complications of MI can be classified according to how they present temporally. Complications of MI that may occur within 1 week include arrhythmias (most commonly ventricular fibrillation and ventricular tachycardia), myocardial rupture, valve incompetence (causing regurgitation) and cardiogenic shock. Later developments include ventricular aneurysm, pericarditis and the aforementioned Dressler’s syndrome.
A Monckeberg arteriosclerosis B Infective endocarditis C Dressler’s syndrome D Dilated cardiomyopathy E Rheumatic heart disease F Left heart failure G Hypertrophic obstructive cardiomyopathy H Aortic stenosis I Carcinoid syndrome A 46-year-old man is referred to the cardiology outpatient clinic. On investigation he is found to have mitral regurgitation and has a past history of St Vitus Dance when he was in school and a mild pericarditis.
E Rheumatic heart disease Rheumatic heart disease (E) is an inflammatory condition most commonly affecting the connective tissue of the heart (but also joints and central nervous system). It occurs several weeks after throat infection with group A β-haemolytic streptococci usually under the age of 10 years. Cardiac complications include endocarditis (causing verroucous lesions of the heart valves); myocarditis (containing Aschkoff-bodies and Anitschow cells causing dilatation of the mitral ring, hence mitral regurgitation); pericarditis (fibrous exudate causing friction rub). Any layer of the heart can be affected, potentially leading to pancarditis. Many years after recovery from acute rheumatic fever, chronic rheumatic heart disease occurs, with fibrosis of the mitral and aortic valves that can occur. The history of St Vitus Dance Suggests Sydenham’s chorea, a well known feature of acute rheumatic fever
A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 40-year-old male presents to his GP with chronic cough with copious amounts of purulent mucus production. High resolution CT scans demonstrate dilated bronchi.
D Bronchiectasis Bronchiectasis (D) is defined as the permanent dilatation of bronchi and bronchioles secondary to chronic inflammation. Causes are numerous, and include chronic pneumonia, for example due to Staphylococcus aureus or Haemophilus influenzae infection, obstructing tumours and cystic fibrosis. Histopathological findings include bronchial wall destruction and transmural inflammation. High-resolution computed tomography (CT) is the diagnostic modality of choice. Abscess formation, haemoptysis and pulmonary hypertension are complications that may arise as a result of bronchiectasis.
A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 14-year-old girl is admitted to hospital after suffering her third bout of pneumonia caused by Pseudomonas aeruginosa infection. She also has a previous admission for pancreatitis.
H Cystic fibrosis Cystic fibrosis (CF; H) is an autosomal recessive condition caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein that primarily affects the exocrine glands. There are several mutations responsible for CF, the most common being ΔF508 mutation. Defective CFTR causes reduced secretion of chloride ions across epithelial cell membranes, resulting in increased sodium and hence water reabsorption into these cells. The result is viscous secretions from exocrine glands affecting multiple organs including the lungs (recurrent infections and bronchiectasis), gastrointestinal tract (distal intestinal obstruction syndrome) and pancreas (pancreatitis).
A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 58-year-old man presents to his GP with haemoptysis and weight loss. He has a 30 pack–year history of smoking. He is referred to the oncologist for a biopsy, who determines ‘oat-shaped’ cells on microscopy.
B Small cell carcinoma Small cell carcinoma (B) is also known as ‘oat-cell’ carcinoma due to the appearance of the malignant cells under the microscope. They appear as nests of small round hyper-chromatic cells that are fragile (chromatin smudging) and possess nuclear moulding. Small cell carcinomas are very aggressive with approximately 80 per cent of cases having metastasized at the time of diagnosis. Small cell carcinomas also express neuroendocrine markers and can cause paraneoplastic syndromes such as Lambert–Eaton myasthenic syndrome. On chest X-rays, the cancer may be seen arising centrally.
A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 62-year-old man presents to his GP with shortness of breath, lethargy and weight loss. The patient’s chest X-ray reveals a peripheral focal lesion in the left lung field.
E Non-small cell carcinoma Non-small cell carcinomas (E) comprise adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Adenocarcinomas are gland forming and therefore will have mucin vacuoles within. This sub-type of non-small cell carcinoma may lead to atypical adenohyperplasia whereby atypical cells are seen to line the alveolar walls; hence adenocarcinoma is usually a peripheral lung cancer. Squamous cell carcinomas are histologically characterized by keratinization and intracellular ‘prickle’ desmosomes. Large cell carcinomas are undifferentiated forms of adenocarcinoma or squamous cell carcinoma.
A Hyaline membrane disease B Small cell carcinoma C Extrinsic allergic alveolitis D Bronchiectasis E Non-small cell carcinoma F Chronic bronchitis G Pulmonary oedema H Cystic fibrosis I Sarcoidosis A 53-year-old woman with a history of rheumatic fever presents to accident and emergency with severe shortness of breath, and has been coughing up pink frothy sputum for the past 2 days.
G Pulmonary oedema Pulmonary oedema (G) is defined as fluid collections in the alveoli which impairs gas exchange that can potentially lead to respiratory failure. Increased hydrostatic pressure causes of pulmonary oedema include heart failure, mitral stenosis, fluid overload and renal failure. Increased capillary permeability can also cause pulmonary oedema, for example due to pneumonia. Chest X-rays can distinguish between cardiac and non-cardiac causes of pulmonary oedema; the former will demonstrate alveolar oedema (bat’s wing appearance), Kerley B-lines, cardiomegaly, upper lobe diversion of blood vessels and effusions.
A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 35-year-old woman is referred to the rheumatology clinic due to recent onset dysphagia. The patient also reports that her fingers have turned very pale and cold. One examination she is found to have tightening of the skin near her finger tips and small dilated vessels on her skin.
G CREST syndrome CREST syndrome (G), also known as limited scleroderma, represents a combination of conditions: calcinosis (calcium deposition in the skin), Raynaud’s disease (vasospasm of blood vessels in response to triggers such as cold), oesophageal dysmotility, sclerodactyly (thickening and tightening of skin surrounding fingers/hands) and telangiectasia (dilation of blood capillaries causing red marks on the surface of the skin). The pathogenesis relates to excessive release of PDGF causing widespread fibroblast activation and multi-organ fibrosis. Chronic fibrosis leads to initimal thickening of the microvasculature known as ‘onion skinning.’
A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 35-year-old woman with a history of recurrent miscarriages presents to her GP with joint pains. Blood tests reveal she is anti-double stranded DNA antibody positive.
A Systemic lupus erythematosus Systemic lupus erythematosus (SLE; A) is a multi-system connective tissue disease that is antinuclear antibody (ANA) positive. The underlying pathology of SLE relates to failure in the regulatory mechanisms of selftolerance. Autoantibodies form against nuclear components such as DNA, RNA and histones. This leads to complement activation and complex formation, which are deposited in organs. Cytology of tissues reveals haematoxylin bodies which are denatured nuclei that are produced when ANA bind to exposed nuclei. LE cells are also visible on microscopy; these are macrophages that have phagocytosed a haematoxylin body.
A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 68-year-old man presents to accident and emergency with symptoms suggestive of heart failure. All initial investigations do not determine an underlying cause. However, a tongue biopsy sample gains an apple-green birefringence under polarized light using Congo red stain.
D Amyloidosis Amyloidosis (D) occurs due to the extracellular deposition of fibrillar proteins that accumulate in tissues and organs. Amyloid proteins arise due to dysfunctional folding resulting in non-branching fibrils. Proteins aggregate into insoluble crossed beta-pleated sheet tertiary conformation. Amyloid proteins contain P-component which causes biopsy samples to characteristically gain an apple-green birefringence using polarized light and Congo red stain. Four major amyloid proteins exist: AA, derived from serum amyloid assisted protein and associated with inflammation; AL, derived from IgG light chains and associated with myeloma; αβ2, linked with Alzheimer’s disease; β2 microglobulin, associated with patients undergoing dialysis treatment.
A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 45-year-old woman presents to accident and emergency with signs suggestive of renal failure. She is found to be p-ANCA positive.
I Microscopic polyangitis Microscopic polyangitis (I) is a small vessel vasculitis affecting the arterioles, venules and capillaries. The pathology involves a trigger factor such as microorganisms and drugs causing immune complex formation in a previously sensitized host. These immune complexes deposit in small vessels leading to neutrophil-related inflammation. Microscopic polyangitis affects the skin, heart, brain and kidneys. Histopathological features of affected vessels include fibrinoid necrosis that leads to fragmented neutrophilic nuclei within vessel walls. Microscopic polyangitis is associated with p-ANCA.
A Systemic lupus erythematosus B Sjögren’s syndrome C Diffuse scleroderma D Amyloidosis E Takayasu arteritis F Dermatomyositis G CREST syndrome H Polymyositis I Microscopic polyangitis A 52-year-old man presents to his GP with limb weakness and shortness of breath. A distinctive rash is noted around both eyes as well as plaques on the joints of his hands.
F Dermatomyositis Dermatomyositis (F) is an inflammatory myopathy that involves skeletal and thoracic muscles. Skeletal muscle involvement will lead to proximal muscle fatigue, especially in the hips and shoulders. Thoracic muscle involvement can affect the lungs (dyspnoea), heart (arrhythmia) and oesophagus (dysmotility). There is, however, sparing of the ocular muscles which differentiates dermatomyositis from myasthenia gravis. Dermatomyositis is also defined by a heliotrope rash (violet erythema around the periorbital region) and Gottron papules (violet scaly plaques over hand joints). Muscle inflammation will also cause an increased blood creatine kinase level.
A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 54-year-old man is seen in the neurology clinic due to tremor and rigidity. A DAT scan reveals reduced uptake in the substantia nigra.
B Parkinson’s disease Parkinson’s disease (B) is a degenerative disorder associated with basal ganglia dysfunction. Clinical features can be remembered by the mnemonic SMART: shuffling gait, mask-like-face, akinesia, rigidity and tremor. Degeneration of the substantia nigra and locus coeruleus of the basal ganglia leads to reduced production of dopamine. At the microscopic level, inclusion bodies known as Lewy bodies are deposited in the cytoplasm of neurons that are made up of α-synuclein. Parkinson’s disease may be associated with Lewy body dementia.
A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 74-year-old man presents to accident and emergency with increasing headache and confusion. The man’s wife suggests her husband may have tripped and fallen 3 days previously.
E Subdural haemorrhage Subdural haemorrhage (E) occurs between the dura and arachnoid due to an acute tear in bridging veins. This tends to occur after a clear history of trauma. Bleeding results in features of raised intracranial pressure. As the bleeding is venous in nature, haematoma development is slow (usually taking 48 hours) and as a result raised intracranial pressure takes time to become apparent. Chronic subdural haemorrhage refers to a re-bleed of a previous bridging vein subdural haemorrhage. Patients will usually present with an altered mental state.
A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 45-year-old woman presents to accident and emergency with the worst headache she has ever experienced. She is noted to have polycystic kidney disease.
A Subarachnoid haemorrhage Subarachnoid haemorrhage (A) occurs in the subarachnoid space. Potential causes include a saccular ‘berry’ aneurysm (most commonly occurring at artery bifurcations of the anterior circulation), hypertension, trauma, arteriovenous malformations and coagulation disorders. Clinical features include a severe ‘thunder clap’ headache radiating to the occiput; this may be preceded by a warning bleed causing a sentinel bleed. Subarachnoid haemorrhages are more commonly associated with polycystic kidney disease, coarctation of the aorta and fibromuscular dysplasia.
A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 35-year-old woman presents to the neurology clinic with weakness of her left side. On examination she is found to have nystagmus and an intention tremor. The patient complains of blurred vision for the past month.
G Multiple sclerosis Multiple sclerosis (MS; G) is a demyelinating disease of the upper motor system which follows a relapsing and remitting course. Histological features along the central nervous system include active (contain lymphocytes and macrophages) and inactive plaques (reduced nuclei and myelin). Clinical features include optic neuritis, intranuclear opthalmoplegia (disruption of medial longitudinal fasciculus) and cerebellar signs, as well as spasticity and weakness of limbs. Variants of MS include Devic disease (a more aggressive form) and Marburg MS (a fulminant form).
A Subarachnoid haemorrhage B Parkinson’s disease C Extradural haemorrhage D Vascular dementia E Subdural haemorrhage F Intracerebral haemorrhage G Multiple sclerosis H Duret haemorrhage I Alzheimer’s disease A 42-year-old man who suffers from Down syndrome is brought to see his GP by his carer. The carer describes how the patient has been wandering out of the house with increased frequency as well as becoming uncharacteristically aggressive, especially in the evening.
I Alzheimer’s disease Alzheimer’s disease (I) is a progressive degenerative disease which mainly occurs in patients over the age of 50 years and the condition is most commonly sporadic. In some instances, there may be a genetic component such as the amyloid precursor protein as well as presenelins 1 and 2 mutations associated with Down syndrome. Inheritance of the ε4 allele of apolipoprotein E increases risk of developing Alzheimer’s disease. Histological features include vascular wall deposition of β-amyloid (amyloid angiopathy), neurofibrillary tangles and neuritic plaques.
A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 35-year-old man has a 3-week history of bloody stools without mucus with associated weight loss. A biopsy of the gastrointestinal tract reveals non-caseating granulomas with transmural inflammation.
H Crohn’s disease Crohn’s disease (H) is an inflammatory bowel disease which can affect any section of the gastrointestinal system. Characteristics include transmural inflammation (full intestinal wall thickness), skip lesions and fistulae. Biospy of the gastrointestinal wall will reveal non-caseating granulomas in approximately 60 per cent of cases. Complications include thickening of the bowel wall (also known as a ‘rubber hose wall’) which can lead to bowel obstruction. Extra-intestinal manifestations of Crohn’s disease include arthritis, ankylosing spondylosis, stomatitis and uveitis, as well as dermatological lesions (pyoderma gangrenosum and erythema nodosum).
A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 24-year-old woman presents to her GP with a 2-week history of diarrhoea, weight loss and fatigue. Biopsy of the gastrointestinal tract reveals villous atrophy with crypt hyperplasia.
D Coeliac disease Coeliac disease (D) is an autoimmune disease that occurs due to gluten sensitivity, specifically gliadin found in wheat, barley and rye. It affects primarily the duodenum and jejunum. CD8+ cells are sensitized to gliadin; they accumulate in the gut and attack enterocytes and as a result villi disappear. As a compensatory mechanism immature enterocytes in the crypts proliferate causing deeper crypts. Therefore, features of gut biopsy samples include intraepithelial lymphocytes, villous atrophy and crypt hyperplasia. Clinical features include steatorrhoea, bloating, weight loss and fatigue (anaemia secondary to malabsorption).
A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 54-year-old man presents to his GP with a 2-week history of worsening dysphagia. The patient’s past medical history reveals severe gastro-oesophageal reflux disease. A duodenoscopy suggests metaplastic transformation of the lower oesophageal region.
F Barrett’s oesophagus Barrett’s oesophagus (F) occurs as a result of chronic gastro-oesophageal reflux disease. At the squamo-columnar junction between the lower oesophagus and stomach, squamous epithelial cells usually exist. Acidity causes transformation of squamous epithelial cells to columnar epithelial cells, a metaplastic change. The metaplastic columnar epithelial cells include goblet cells that produce intestinal mucin; hence the process is termed intestinal metaplasia. The major complication of Barrett’s oesophagus is an increased risk of adenocarcinoma of the oesophagus.
A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 45-year-old man is referred to the gastroenterology outpatient clinic due to severe epigastric pain and an episode of haematemesis. Further testing reveals he is Helicobacter pylori positive and has a 20 pack–year history of smoking.
I Peptic ulcer disease Peptic ulcer disease (I) can either be duodenal or gastric. Ulcers differ from erosions as they extend to the submucosa (sometimes to the muscularis mucosa) and take weeks to heal, whereas erosions breach the mucosa only and take days to heal. The main causes of peptic ulcers are Helicobacter pylori, NSAIDs, Zollinger–Ellison syndrome and smoking. These factors disrupt the balance between protective (mucus layer and bicarbonate secretion) and damaging (acid and enzymes) elements leading to ulceration.
A Ulcerative colitis B Chronic gastritis C Oesophageal cancer D Coeliac disease E Gastric carcinoma F Barrett’s oesophagus G Gardener’s syndrome H Crohn’s disease I Peptic ulcer disease A 56-year-old man presents to his GP with abdominal pain, weight loss and fatigue. A duodenoscopy allows a biopsy of a gastric lesion to be taken, which demonstrates signet ring cells and linitis plastica.
E Gastric carcinoma Gastric carcinoma (E) is usually a consequence of chronic gastritis and hence Helicobacter pylori is implicated in the pathogenesis. H. pylori causes intestinal metaplasia leading to gastric atrophy which becomes dysplasia and eventually carcinoma. On histology the carcinoma can be ulcer-like, but differs from peptic ulcers as they have irregular borders and raised edges. Features of gastric carcinoma are the presence of signet ring cells (cells with compressed nuclei) and linitis plastica (the stomach becomes thick and rigid resembling a leather bottle).
A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 56-year-old man with previous history of hepatitis C infection presents to accident and emergency with jaundice. His wife notes that he has recently been bruising very easily. Ultrasound of the patient’s liver reveals irregular echogenicity demonstrating nodules.
B Cirrhosis Cirrhosis (B) is defined as the diffuse fibrosis of the liver with abnormal architecture characterized by nodules secondary to chronic hepatic disease. This can be sub-classified as macronodular (3 mm; usually viral aetiology). Fibrosis results from stellate cell activation, which deposit collagen. Nodules represent proliferating hepatocytes that lack normal acinar structure and hence have a haphazard blood supply; this leads to shunt formation and portal hypertension. Causes of cirrhosis include alcohol, hepatitis B and C, primary biliary cirrhosis, haemochromatosis, Wilson’s disease and α1-antitrypsin deficiency.
A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 35-year-old man presents to his GP with his mother with signs of Parkinsonism (tremor, rigidity and slow movement) as well as recent changes in his behaviour.
I Wilson’s disease Wilson’s disease (I) is an autosomal recessive condition that results from a mutation in the ATP7B gene leading to multi-organ copper accumulation. ATP7B is a protein that facilitates the transport of copper across cell membranes. Liver involvement will lead to cirrhosis, most commonly in children, whilst accumulation in the brain can lead to Parkinsonism, seizures and dementia. Psychological features include behavioural changes, depression and psychosis. Other organs affected include the eyes (Kayser–Fleischer rings), kidneys (renal tubular acidosis) and heart (cardiomyopathy).
A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 56-year-old woman is investigated by the hepatology team for decompensated liver disease. A liver biopsy sample stains blue with Perl’s Prussian blue stain.
F Haemochromatosis Haemochromatosis (F) is an autosomal recessive condition that is due to a mutation in the HFE gene. The HFE protein regulates iron absorption that is stored as haemosiderin. Histological features of haemochromatosis include a golden-brown haemosiderin deposition in the parenchyma of many organs. Haemosiderin eventually leads to inflammation and subsequent fibrosis. Histological samples of affected tissue will stain blue with Perl’s Prussian blue. Organs affected include the liver (cirrhosis), pancreas (diabetes), skin (bronzed pigmentation), heart (cardiomyopathy) and gonads (atrophy and impotence).
A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 53-year-old man who has recently emigrated from sub-Saharan Africa is referred to the hepatology department due to recent onset weight loss, jaundice and ascites. There is history of previous aflatoxin exposure.
G Hepatocellular carcinoma Hepatocellular carcinoma (HCC; G) is the most prevalent primary liver malignancy. Most commonly HCC occurs secondary to cirrhosis. The risk factors for HCC are therefore the numerous causes of cirrhosis. However, carcinogens such as aflatoxin, produced by the fungal genus Aspergillus can directly cause HCC; aflatoxin contaminates many crops in the developing world, notably cereals and nuts. α-Fetoprotein is a marker that may suggest the presence of HCC. There is also evidence that the metabolic syndrome contributes to risk of developing HCC.
A Cholangiocarcinoma B Cirrhosis C α1-Antitrypsin deficiency D Haemosiderosis E Primary biliary cirrhosis F Haemochromatosis G Hepatocellular carcinoma H Primary sclerosing cholangitis I Wilson’s disease A 45-year-old woman presents to accident and emergency with jaundice and pruritis. Xanthelasma are noted on examination. The patient is found to be antimitochondrial antibody positive.
E Primary biliary cirrhosis Primary biliary cirrhosis (PBC; E) is an autoimmune disease of the liver, affecting the small and medium-sized intra-hepatic ducts. The primary histological feature is the dense accumulation of lymphocytes around bile ducts creating granulomas and total destruction of the ducts. This results in an obstructive cholestasis causing the triad of jaundice, xanthelasma (cholesterol is normally excreted in bile) and pruritis. Biochemically PBC is linked with anti-mitochondrial antibodies, as well as raised ALP, GGT, IgM and cholesterol. PBC is also strongly associated with Sjögren’s syndrome.
A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 65-year-old man presents to his GP with blisters along his left arm that are about 1.0 cm in diameter. Gentle rubbing of the affected area does not lead to skin exfoliation.
A Pemphigoid Pemphigoid (A) is an autoimmune deep bullous (blisters >0.5 cm) condition that occurs in the elderly. Bullae are fluid filled and therefore do not rupture easily; pemphigoid is Nikolsky sign negative. The underlying pathology involves IgG binding to hemi-desmosomes. This causes activation of eosinophils that are recruited to the area. Pemphigoid should not be confused with pemphigus (option J), also an autoimmune bullous disease that affects middle-aged patients, causing superficial bullae on the skin (Nikolsky positive). IgG bind to desmosomes in the intra-epidermal region resulting in acantholysis.
A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 38-year-old man on the respiratory ward has been diagnosed with Mycoplasma pneumoniae and develops a number of target shaped rashes on his body.
H Erythema multiforme Erythema multiforme (H) is a hypersensitivity reaction secondary to infections (herpes simplex, mycoplasmas and fungi) and drugs (penicillin, phenytoin and barbiturates). The pathogenesis is unclear but is thought to be due to immune-complex deposition in the microvasculature of the skin and oral mucous membranes. Most commonly the rash is self-limiting and target shaped as well as being maculo-papular with sub-epidermal bullae in the centre. In severe cases, the rash may involve mucosal surfaces leading to Steven–Johnson’s syndrome, characterized by epidermal necrosis with minimal inflammatory cell infiltrate.
A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 45-year-old woman presents to her GP with salmon-pink plaques with a silver– white scale on the extensor surfaces of her elbows.
F Psoriasis Psoriasis (F) is an autoimmune condition primarily affecting the extensor surfaces of the skin. Histological features include parakeratosis (corneum nuclei mixed with keratin to form a thick keratin layer creating ‘silvery scales’); Munro-abscesses (white blood cells entering the corneum); loss of the granular layer leading to pin-point bleeding (Auspitz sign); clubbing of the rete ridges, whereby they grow downwards leading to a ‘test-tubes in a rack’ appearance. Clinical features include salmon-pink plaques with a silver–white scale on the skin and onycholysis.
A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 54-year-old man is referred to the dermatologist with a brown warty lesion on his nose which has a rough consistency. Biopsy of the lesion reveals solar elastosis.
E Actinic keratosis Actinic keratosis (solar keratosis; E) is defined as epidermal dysplasia that occurs secondary to sunlight and presents as a brown–red warty lesion with a sandpaper-like consistency. Histological features include solar elastosis, focal parakeratosis, atypical cells and inflammatory cell infiltrates. Actinic keratosis does not affect the full thickness of the epidermis. It is a premalignant condition that may progress to squamous cell carcinoma in approximately 20 per cent of cases.
A Pemphigoid B Bowen’s disease C Pityriasis rosea D Lichen planus E Actinic keratosis F Psoriasis G Basal cell carcinoma H Erythema multiforme I Malignant melanoma J Pemphigus A 59-year-old woman presents to her dermatologist with a 3 cm black irregular lesion on her cheek. Over the next month the lesion spreads to cover 6 cm with new onset pain.
I Malignant melanoma Malignant melanoma (I) is a malignant tumour of melanocytes. The characteristic features can be remembered by the mnemonic ABCDE: asymmetry, border irregularity, colour (usually black; sometimes demonstrate colours of the French flag), diameter >5 cm and evolution (change in size, colour and/or new onset itchiness/pain). Malignant melanomas initially grow radially in situ within the epidermis; over time there is growth vertically into the dermis, eventually leading to metastases. Sub-types include lentigomaligna (LM), acrallentigious (AL), superficial spreading (SS) and nodular (N).
A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 45-year-old man presents to accident and emergency with haematuria and admits to passing less urine than previously. He is found to be hypertensive. Microscopy of the patient’s urine reveals red and white cell casts.
A Nephritic syndrome Nephritic syndrome (A) involves the following: haematuria, red cell and white cell casts, dysmorphic red cells, oliguria and hypertension. The pathogenesis begins with inflammation of glomerular vessels allowing red blood cells to enter the renal tubule; as they enter they are damaged. The body compensates for the inflammation by slowing renal blood flow causing oliguria, which leads to water retention and hence hypertension. Cellular casts form as a result of Tamm–Horsefall secretions in the distal collecting duct and collecting duct that ‘glue’ cells together, hence forming a cast.
A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 42-year-old man presents to accident and emergency with an episode of haemoptysis and haematuria. Blood tests reveal he is in acute renal failure. Once the patient is stable a renal biopsy demonstrates a crescent morphology on immunofluorescence.
F Goodpasture’s syndrome Goodpasture’s syndrome (F) is an anti-glomerular basement membrane disease that causes rapidly progressive glomerulonephritis (RPGN). RPGN all demonstrate a crescent sign on biopsy, which represents the proliferation of macrophages and parietal cells in the Bowman’s space. There are numerous causes of RPGN; these can be differentiated by looking at the IgG and C3 deposition pattern on immunofluorescence. Goodpasture’s syndrome occurs due to IgG against the A3 chain of type-4 collagen, creating a linear pattern on immunofluorescence.
A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 64-year-old man on the Care of the Elderly ward is found to be in acute renal failure secondary to statin-related rhabdomyolysis. Urinalysis reveals the presence of ‘muddy’ casts.
D Acute tubular necrosis Acute tubular necrosis (D) is defined as damage to the tubular epithelium leading to acute renal failure. Ischaemic or toxic injury reduces GFR in three ways: 1) Loss of polarity (loss of membrane channels reduces sodium reabsorption; more sodium reaches macula densa constricting afferent arteriole, hence reducing GFR); 2) Glomerular backpressure (formation of casts in distal convoluted tubule creates backpressure reducing GFR); and 3) Interstitial leakage (back-pressure forces fluid into interstitium causing swelling and compression of tubules).
A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis An 8-year-old girl presents to accident and emergency with frank haematuria. Her parents state that she had just recovered from a throat infection 2 days previously.
G IgA nephropathy IgA nephropathy (Berger’s disease; G) usually occurs 1–4 days after a respiratory or gastrointestinal infection (mucosal defence is primarily IgA). IgA is deposited in the mesangium which may lead to RPGN. On immunofluorescence a granular staining of IgG and C3 will demonstrate IgA nephropathy (other conditions causing this pattern are SLE, Henoch–Schlönein purpura, post-streptococcal infection and Alport’s syndrome). There is frank haematuria in 50 per cent of cases and microscopic haematuria in 50 per cent of patients.
A Nephritic syndrome B Wegener’s granulomatosis C Membranous glomerulonephritis D Acute tubular necrosis E Minimal change glomerulonephritis F Goodpasture’s syndrome G IgA nephropathy H Nephrotic syndrome I Focal segmental glomerulonephritis A 62-year-old woman on the Care of the Elderly ward is found to have new onset ankle swelling. A urine dipstick demonstrates proteinuria
H Nephrotic syndrome Nephrotic syndrome (H) is the combination of proteinuria, hypoalbuminaemia and oedema (with associated hyperlipidaemia and lipiduria). Primary causes such as IgA nephropathy are most common in children, whereas systemic causes such as diabetes and SLE are more common in adults. Damage to the glomerulus causes increased permeability and hence proteins pass into the tubules leading to proteinuria and hypoalbuminaemia. A reduced oncotic pressure therefore causes oedema. The liver compensates by producing increased amounts of lipids which are then excreted via the damaged kidneys causing lipiduria.
