Pathology 8 Flashcards

Question

Tumour lysis syndrome

Answer 1

Tumour lysis syndrome is a common oncological emergency. It is associated with rapid cell death on starting chemotherapy and is common in tumours which are rapidly proliferating. These are classically haematological malignancies such as leukaemia and lymphoma. Clinical features It results in an increase in serum urate, potassium and phosphate, precipitating renal failure. Common symptoms include nausea, vomiting and muscle pain. Management Management focuses on preventing this from occurring through giving prophylactic allopurinol and in some cases a recombinant urate oxidase, rasburicase. Good hydration should be maintained.

Answer 2

Achalasia is a condition of unknown aetiology which causes failure of the lower oesophageal sphincter to relax. Epidemiology It is an uncommon condition with an incidence of 1.6 cases per 100,000 individuals. It equally affects men and women. A small percentage of cases are associated with underlying oesophageal cancer. Presentation of achalasia Dysphagia – gradual onset (months to years) Regurgitation of undigested food Aspiration Retrosternal chest pain / heartburn – often does not respond to PPI Weight loss – often mild Investigations Endoscopy – may show dilated oesophagus, containing residual material. It also rules out other more sinister pathologies. Oesophageal manometry – shows high pressure and incomplete lower oesophageal sphincter relaxation Barium swallow – shows classic 'bird's beak appearance' in advanced disease Treatments Medical Botulinum toxin injections (botox) Medical therapy can be tried (calcium channel blockers / nitrites) in patients who fail botox therapy or are not suitable surgical candidates Surgery: Options include oesophageal dilatation and surgical cleavage of the muscle, called 'Heller's Myotomy'. Heller's cardiomyotomy This is the correct answer. This patient is displaying signs and symptoms of achalasia, failure of the lower oesophageal sphincter to relax due to degeneration of the myenteric plexus. Patients present with difficulty swallowing both liquids and swallows, in contrast to patients with an obstruction who present with difficulty swallowing solids first. The best treatment for this condition is a Heller's cardiomyotomy which is a surgical procedure where the muscle fibers of the lower oesophagus are divided.

Answer 3

Polyhydramnios is the presence of too much amniotic fluid in the uterus. Clinical features Polyhydramnios may present with a uterus which feels tense or large for dates and it may be difficult to feel the foetal parts on palpation of the abdomen. In many cases of polyhydramnios there is no identifiable cause. Causes Causes of polyhydramnios can be due to excessive production of amniotic fluid or insufficient removal of amniotic fluid. Excess production can be due to increased foetal urination: Maternal diabetes mellitus Foetal renal disorders Foetal anaemia Twin-to-twin transfusion syndrome Insufficient removal can be due to reduced foetal swallowing: Oesophageal or duodenal atresia Diaphragmatic hernia Anencephaly Chromosomal disorders Complications of polyhydramnios Complications of polyhydramnios can be divided into maternal and foetal. Maternal complications Maternal respiratory compromise due to increased pressure on the diaphragm Increased risk of urinary tract infections due to increased pressure on the urinary system Worsening of other symptoms associated with pregnancy such as gastro-oesophageal reflux, constipation, peripheral oedema and stretch marks Increased incidence of caesarean section delivery Increased risk of amniotic fluid embolism (although this is rare) Foetal complications Pre-term labour and delivery Premature rupture of membranes Placental abruption Malpresentation of the foetus (the foetus has more space to “move” within the uterus) Umbilical cord prolapse (polyhydramnios can prevent the foetus from engaging with the pelvis, thus leaving room for the cord to prolapse out of the uterus before the presenting part) Management Treatment includes management of any underlying causes (e.g. in maternal diabetes) and amnio-reduction in severe cases. Smoking can cause placental insufficiency which can lead to intrauterine growth restriction and oligohydramnios (not polyhydramnios).

Answer 4

A ptechial rash may occur in meningococcal septicaemia. Although meningococcal septicaemia can cause headache, the history of a sudden onset 'thunderclap' headache followed by collapse is suggestive of sub-arachnoid haemorrhage

Answer 5

Jaundice and ascites occur in decompensated chronic liver disease. Decompensated chronic liver disease may cause hepatic encephalopathy, resulting in a progressive impairment in consciousness. The history of a 'thunderclap' headache along with the family history of chronic kidney disease suggests sub-arachnoid haemorrhage secondary to ruptured berry aneurysm, a common association with polycystic kidney disease.

Answer 6

Spontaneous upbeat nystagmus may be present in Wernicke's encephalopathy, a condition caused by vitamin B1 deficiency. Wernicke's encephalopathy presents with the triad of ataxia, confusion, and oculomotor impairment. The clinical case does not describe any risk factors for vitamin B1 deficiency (such as chronic alcoholism, malnutrition, bariatric surgery, or hyperemesis gravidarum).

Answer 7

This is the correct answer. The patient presents with sub-arachnoid haemorrhage secondary to a ruptured berry aneurysm. This is associated with polycystic kidney disease, felt as bilateral flank masses on examination. The family history of chronic kidney disease is consistent with polycystic kidney disease, an autosomal dominant disorder caused by mutation in the PKD1 gene of chromosome 16.

Answer 8

Pinpoint pupils are indicative of opiate overdose. There are no clues in the question to suggest heroin abuse, such as track marks in the forearms or a history of substance misuse. The history of a sudden onset 'thunderclap' headache points towards a sub-arachnoid haemorrhage.

Answer 9

ABCDE Assessment Blood pressure may be high in hypertensive encephalopathy, or low in hypovolaemic shock. Core temperature is low in hypothermia. Examination of the skin may reveal jaundice, suggestive of hepatic encephalopathy, or petechial rash, suggestive of meningococcal sepsis. Close examination of the head/face should be done to check for signs of a basal skull fracture (with haemotympanum, Battle's sign, racoon eyes, and CSF rhinorrhoea/otorrhoea). Glasgow Coma Scale The Glasgow Coma Scale should be determined to grade the severity of the impairment in consciousness. Eye response (out of 4.: 4 open spontaneously, 3 open to voice, 2 open to pain, 1 do not open. Verbal response (out of 5): 5 oriented, 4 confused, 3 inappropriate words, 2 incomprehensible sounds, 1 no sounds. Motor response (out of 6): 6 obeys command, 5 localises to pain, 4 withdraws to pain, 3 abnormal flexion to pain, 2 extension to pain, 1 no movement. The threshold for intubation and ventilation is often quoted as GCS of 8 or less (but this can vary according to the clinical situation) Further Examination in Coma A focused neurological examination should be carried out to localise the anatomical site of the coma. It is important to be aware of Cushing's triad, suggestive of imminent herniation: bradycardia, hypertension, and irregular breathing. This should prompt urgent neurosurgical review. Oculomotor signs of herniation include: gaze preference to 1 side initially, dilation of the pupil ipsilateral to the lesion (due to stretching of the third cranial nerve), followed by loss of pupillary reactivity due to herniation and midbrain damage. The pupils can also be helpful in determining the aetiology of the coma - e.g. pinpoint pupils may indicate opiate overdose.

Answer 10

Serum lipase This is the correct answer. This patient is displaying signs and symptoms of acute pancreatitis, which is a common diagnosis in individuals with a history of alcohol excess. A serum lipase will be at least 3 times the upper limit of normal in a diagnosis of pancreatitis, and is specific to this condition. Bilirubin This is the incorrect answer. Bilirubin is raised in patients with jaundice, which maybe be caused by a number of conditions including haemolysis, obstruction and acute hepatitis. It will not be diagnostic in this patient. Gamma GT This is the incorrect answer. A gamma GT level is likely to be raised in a patient with a history of alcohol excess, but is unlikely to give a diagnosis in this patient, as it is non-specific. Pancreatitis is a common presentation to the acute surgical take. It is associated with a high morbidity and mortality especially if identified late. It is therefore a critical differential diagnosis for many patients presenting with abdominal pain. Causes of acute pancreatitis Causes can be remembered with the mnemonic GET SMASHED: ``` Gallstones (most common worldwide) Ethanol (most common cause in Europe) Trauma Steroids Mumps Autoimmune disease (Polyarteritis Nodosa/SLE) Scorpion bite (!) Hypercalcaemia, hypertriglycerideaemia, hypothermia ERCP Drugs (as above) Causes of drug-induced pancreatitis A good mnemonic for drug-induced pancreatitis is FATSHEEP: ``` ``` Furosemide Azathioprine/Asparaginase Thiazides/Tetracycline Statins/Sulfonamides/Sodium Valproate Hydrochlorothiazide Estrogens Ethanol Protease inhibitors and NRTIs There is some overlap here as some of the drugs listed are sulphonamides. ``` Thiazides, furosemide, some HIV drugs (protease inhibitors and non-nucleoside reverse transcriptase inhibitors), sulfasalazine and gliclizide are all classed as sulphonamides due to their sulphonamide group.

Answer 11

Symptoms Acute pancreatitis is associated with a stabbing-like, epigastric pain which radiates to the back that is relieved by sitting forward or lying in the fetal position. Vomiting is highly associated with this. Importantly, past medical history and social history is vital. A recent alcoholic binge or a history of gallstones are highly suggestive. Signs Signs can be variable. Look for symptoms of hypovolaemia (tachycardia, dry mucous membranes due to third-space losses of fluid. Fever is only present if pancreatitis has been complicated with infection There may be guarding in the epigastric region, however, these are relatively non-specific signs. Haemorrhagic pancreatitis although rare shows signs that are Grey-Turner's sign is known as bruising along the flanks and indicates retroperitoneal bleeding which is highly associated with acute pancreatitis. Cullen's sign indicates bruising around the peri-umbilical area which again is highly associated with pancreatitis. Third space fluid sequestration in pancreatitis is the result of a combination of inflammatory mediators, vasoactive mediators and tissues which lead to vascular injury, vasoconstriction and increased capillary permeability leading to extravasation of fluid into the third space. This can lead to ARDS (Acute Respiratory Distress Syndrome), pleural effusions and hypovolaemia leading to AKI (Acute Kidney Injury). Bloods FBC and Urea and Electrolyes Leukocytosis can indicate the presence of necrotising pancreatitis. LFT's may also be abnormal if there is gallstone disease. - Lipase is a more sensitive and specific marker than amylase and should be used if available. However, it should be noted that it is often not readily available in UK hospitals An amylase 3x the upper limit of normal is extremely suggestive of acute pancreatitis. Importantly, the degree of elevation of amylase is not related to the severity of the disease. However, other causes such as perforated duodenal ulcer, cholecystitis and mesenteric infarction may also elevate amylase although to a lesser extent. Imaging investigations Imaging tests are not useful for the diagnosis of pancreatitis, but may be useful to identify causes. Ultrasound abdomen can look for gallstones. MRCP can be used to look for obstructive pancreatitis. ERCP is often preferred in these cases compared to MRCP and can be therapeutic. A CT scan can be performed to at a later stage if complications of pancreatitis are suspected such as pseudocysts or necrotizing pancreatitis. Severity of pancreatitis The modified Glasgow criteria are used to predict the severity of pancreatitis. In practice this is usually done at admission and after 48 hours of admission. The true score is performed after 48 hours. A score of 3 or more positive factors indicates transfer to ITU/HDU for intensive monitoring and aggressive fluid resuscitation. These indicators are based on the degree of potential complications arising from pancreatitis, such as necrosis of surrounding tissue and therefore saponification, reduced hormone output (insulin) and ARDS. It can be remembered by the mnemonic PANCREAS: ``` PaO2 < 8kPa (60mmHg) Age > 55 years Neutrophils - WBC >15 x109/l Calcium < 2mmol/l Renal function - Urea > 16mmol/l Enzymes - AST/ALT > 200 iu/L or LDH > 600 iu/L Albumin < 32g/l Sugar - Glucose >10mmol/L ```

Answer 12

Management The management of pancreatitis is to help maintain electrolyte imbalances and compensate for the third space losses seen in this disease. Supportive care is the main way of facilitating this – Aggressive fluid resuscitation with crystalloids Aim to keep urine output > 30 mL/hour Start with a 1 litre bolus and try to maintain adequate urine output. This usually amount to a fluid requirement of 3 – 5 ml/kg/hr Catheterisation Analgesia Strong analgesia in the form of opioids are needed Anti-emetics IV antibiotics are shown to have no real effect in outcome unless necrotising pancreatitis is present. Necrotising pancreatitis is a complication of severe pancreatitis representing inadequate fluid resuscitation during initial management. It is usually diagnosed by CT scan. Routinely giving antibiotics in pancreatitis is not current clinic practice. Calcium may be given if hypocalcaemia is present, but is not prescribed prophylactically. Insulin may also be given in the presence of hyperglycaemia due to the damaged pancreas reducing release of the hormone.

Answer 13

Review again in 2 weeks- This patient is presenting to the GP with a common cold and a soft systolic murmur at the left sternal edge. This is most likely to be an innocent murmur. Innocent murmurs are very common in children (up to 30% of children at some point), and can be precipitated by febrile illness. As this child currently has a mild viral infection, the best option is to review the murmur in a few weeks once the infection has resolved, to see if the murmur has disappeared with the infection. The infection is likely to be a mild viral upper respiratory tract infection, as evidenced by a lack of tonsillar exudate, angry red throat and no sign of ear infection (bulging tympanic membrane with effusion). Innocent murmurs are very common benign murmurs that occur in around a third of children at some point during childhood. Features The features of 'innoSent' murmurs all start with the letter S: Soft Systolic murmur at the left Sternal edge in an a Symptomatic patient. Management Innocent murmurs can be made more prominent when children have a febrile illness. If a murmur like this is discovered when a child has a febrile illness, the best option is to review the child in a few weeks. This will allow assessment of the murmur to see if it has resolved with the infection, in keeping with an innocent murmur. If the murmur persists, then further investigation (e.g. echocardiogram) could be considered.

Answer 14

Complications after relieving outflow obstruction Differentiating chronic and acute urinary retention Chronic urinary retention differs from acute urinary retention by the absence of pain or urge to urinate. It has developed over a prolonged period of time. Differentiating low from high pressure urinary retention Chronic urinary retention can be differentiated into low or high pressure, by the presence of detrusor activity. Detrusor activity causes high pressure chronic retention which increases the risk of renal damage, high blood pressure and upper renal tract damage. Complications of relieving urinary retention Upon relieving urinary obstruction, there's likely to be a diuresis which is a physiological response to retained sodium, water and urea. Development of post obstructive diuresis occurs when there's >200ml/hr for 2 consecutive hours. Management of post obstruction diuresis Urine osmolarities should be taken as this will determine management. Iso-osmolar urine indicated the kidneys do not need to concentrate the urine and is consistent with physiological diuresis and it generally self-limiting. Hyper-osmolarity indicates the kidneys are concentrating urine so post-obstructive diuresis has, or is resolving. Hypo-osmolarity indicates salt wasting and the inability for the kidneys to concentrate urine. This is pathological and patients should have fluids replaced like for like.

Answer 15

Morphine causes depression of the respiratory centres leading to decreased respiration. This in turn leads to a build up of carbon dioxide (causing acidosis) and reduces oxygenation (causing hypoxia). Morphine also constricts the pupils.

Answer 16

Furosemide and Spironolactone First line management in a patient with heart failure and preserved ejection fraction (HFPEF) would be lifestyle advice, low dose diuretic in patients with signs of fluid overload and ACE-inhibitor/ARB if the patient is hypertensive. Furosemide is indicated, however, spironolactone is used in patients with heart failure with reduced ejection fraction (HFPEF) and is a second line treatment option. 5% Sacubitril/Valsartan First line management in a patient with heart failure and preserved ejection fraction (HFPEF) would be lifestyle advice, low dose diuretic in patients with signs of fluid overload and ACE- inhibitor/ARB if the patient is hypertensive. Sacubitril/Valsartan is a relative new heart failure ACE-inhibitor/ARB combination drug but it is indicated in patients with reduced ejection fraction and symptoms corresponding to NYHA II-IV 3% Furosemide and Bisoprolol First line management in a patient with heart failure and preserved ejection fraction (HFPEF) would be lifestyle advice, low dose diuretic in patients with signs of fluid overload and ACE- inhibitor/ARB if the patient is hypertensive. Furosemide is indicated, however, beta blockers used in patients with heart failure with reduced ejection fraction (HFPEF). Bisoprolol would also be a relative contraindication given his history of asthma. 12% Furosemide and Rampril This is the correct answer. First line management in a patient with heart failure and preserved ejection fraction (HFPEF) would be lifestyle advice for risk factor reduction, low dose diuretic in patients with signs of fluid overload and ACE- inhibitor/ARB if the patient is hypertensive. 61% Ramipril and Spironolactone First line management in a patient with heart failure and preserved ejection fraction (HFPEF) would be lifestyle advice, low dose diuretic in patients with signs of fluid overload and ACE- inhibitor/ARB if the patient is hypertensive. Ramipril is indicated, however, spironolactone is used in patients with heart failure with reduced ejection fraction (HFPEF) and is a second line treatment option. ``` Causes of systolic heart failure Ischaemic heart disease Dilated cardiomyopathy Myocarditis Infiltration (e.g. in haemochromatosis or sarcoidosis) Causes of diastolic heart failure Hypertrophic obstructive cardiomyopathy Restrictive cardiomyopathy Cardiac tamponade Constrictive pericarditis High output cardiac failure definition Heart failure is defined as failure of the heart to generate sufficient cardiac output to meet the metabolic demands of the body. ``` In high output cardiac failure cardiac output is normal, but there is an increase in peripheral metabolic demands which exceed those that can be met with maximal cardiac output. Causes of high output cardiac failure Causes of high output cardiac failure can be remembered by the mnemonic AAPPTT: ``` Anaemia Arteriovenous malformation Paget's disease Pregnancy Thyrotoxicosis Thiamine deficiency (wet Beri-Beri) Clinical features of left heart failure Left heart failure causes pulmonary congestion (pressure builds up behind the left heart i.e. in the lungs) and systemic hypoperfusion (reduced left heart output). ``` NB: Sometimes left sided heart failure can lead to pulmonary congestion which in turn also pushes the right ventricle into failure. In these cases signs and symptoms of both left and right sided heart failure may be present. Symptoms caused by pulmonary congestion Shortness of breath on exertion Orthopnoea Paroxysmal nocturnal dyspnoea Nocturnal cough (± pink frothy sputum) Signs caused by pulmonary congestion Tachypnoea Bibasal fine crackles on auscultation of the lungs Signs caused by systemic hypoperfusion Cyanosis Prolonged capillary refill time Hypotension Less common signs of left heart failure Pulsus alternans (an alternating strong and weak pulse) S3 gallop rhythm (due to filling of a stiffened ventricle) Features of functional mitral regurgitation Clinical features of right heart failure Right heart failure causes venous congestion (pressure builds up behind the right heart) and pulmonary hypoperfusion (reduced right heart output). ``` Symptoms caused by venous congestion Ankle swelling Weight gain Abdominal distension and discomfort, Anorexia/nausea. Signs caused by venous congestion Raised JVP Pitting ankle/sacral oedema Tender smooth hepatomegaly Ascites Transudative pleural effusions (typically bilateral) New York Heart Association Classification of Heart failure The NYHA Classification system is used to classify severity of cardiovascular disability through severity of exertional dyspnoea limiting activity, or discomfort at rest. It runs from Class I (no limitation) to Class IV (discomfort at rest). ``` Class I - no limitation in physical activity, and activity does not cause undue fatigue, palpitation or dyspnoea. Class II - slight limitation of physical activity, and comfort at rest. Ordinary physical activity causes fatigue, palpitation and/or dyspnoea. Class III - marked limitation in physical activity, but comfort at rest. Minimal physical activity causes fatigue (less than ordinary). Class IV - inability to carry on any physical activity without discomfort, with symptoms occurring at rest. If any activity takes place, discomfort increases. Investigations in heart failure Investigations depends on the presentation of the patient. In a patient presenting to the general practitioner with suspected heart failure investigations should be carried out as follows: ECG features This may be normal or reveal clues as to the underlying cause of the heart failure (e.g. ischaemic changes or arrhythmias). NT-proBNP interpretation BNP is released by the ventricles in response to myocardial stretch. BNP has a high negative predictive value, so if the BNP is not raised the diagnosis of congestive cardiac failure is highly unlikely. If the BNP is raised, the patient should be referred for trans-thoracic echocardiogram. If BNP>2000ng/L the patient needs an urgent 2 week referral for specialist assessment and an ECHO. If BNP 400-2000ng/L the patient should get a 6 week referral for specialist assessment and an ECHO. Echocardiogram interpretation Echocardiogram will confirm the presence and degree of ventricular dysfunction. Ventricular dysfunction is normally measured by the ejection fraction. <40% = heart failure is reduced ejection fraction Greater than 40% but raised BNP = Heart failure with preserved ejection fraction Blood tests U+Es to assess renal function (for medication) and to look for hyponatraemia LFTs for hepatic congestion TFTs to check for hyperthyroidism Glucose and lipid profile to assess modifiable cardiovascular risk factors BNP is significantly associated with a diagnosis of heart failuare Chest Xray findings Chest x-ray findings in heart failure can be remembered by the ABCDEF mnemonic: A: Alveolar oedema (with 'batwing' perihilar shadowing) B: Kerley B lines (caused by interstitial oedema) C: Cardiomegaly (cardiothoracic ratio >0.5) D: upper lobe blood diversion E: Pleural effusions (typically bilateral transudates) F: Fluid in the horizontal fissure Lifestyle modification Smoking cessation Salt and fluid restriction (this improves mortality) Supervised cardiac rehabilitation Pharmacological management ACE-inhibitor and beta-blocker (these improve mortality) Consider angiotensin receptor blocker (ARB) if intolerant to ACE inhibitors Consider hydralazine and a nitrate intolerant to ACE-I and ARB. Loop diuretics such as furosemide or bumetanide improve symptoms (but NOT mortality) If symptoms persist and NYHA Class 3 or 4 consider: Aldosterone antagonists such as spironolactone or eplerenone. These drugs also improve mortality. Hydralazine and a nitrate for Afro-Caribbean patients Ivabradine if in sinus rhythm and impaired ejection fraction Angiotensin receptor blocker Digoxin - useful in those with AF. This worsens mortality but improves morbidity. Surgical/device management options Cardiac resynchronisation therapy ICDs are indicated if the following criteria are fulfilled: QRS interval <120ms, high risk sudden cardiac death, NYHA class I-III QRS interval 120-149ms without LBBB, NYHA class I-III QRS interval 120-149ms with LBBB, NYHA class I Initial Management of acute heart failure (pulmonary oedema) Sit the patient up Oxygen therapy (aiming saturations >94% in normal circumstances) IV furosemide 40mg or more (with further doses as necessary) and close fluid balance (aiming for a negative balance) SC morphine - this is contentious with some studies suggesting that it might increase mortality by suppressing respiration Advanced management of acute heart failure (pulmonary oedema) The following usually occurs in a high dependency or ITU setting. CPAP - reduces hypoxia and may help push fluid out of alveoli Intubation and ventilation Furosemide infusion - continuous IV furosemide given over 24 hours to maximise diuresis Dopamine infusion - Continuous IV dopamine given over 24 hours. It works by inhibiting sympathetic drive and thereby increasing myocardial contractility. Intra-aortic balloon pump - if the patient is in cardiogenic shock Ultrafiltration - If resistant to or contraindicated diuretics Note that GTN infusion is no longer routinely used in acute heart failure Adverse effects of heart failure medications Common adverse effects for different medications are listed below Beta blockers: Bradycardia, hypotension, fatigue, dizziness ACE inhibitors: Hyperkalaemia, renal impairment, dry cough, lightheadedness, fatigue, GI disturbances, angioedema Spironolactone: Hyperkalaemia, renal impairment, gynaecomastia, breast tenderness/hair growth in women, changes in libido Furosemide: Hypotension, hypoatraemia/kalaemia, Hydralazine/nitrate: Headache, palpitation, flushing Digoxin: Dizziness, blurred vision, GI disturbances

Answer 17

Hyperuricaemia may be caused by increased urate production or impaired urate excretion. Causes Increased production ``` Tumour lysis (particularly lymphoma and leukaemia) Haemolysis Psoriasis Rhabdomyolysis Decreased excretion ``` ``` Primary gout Chronic kidney disease Thiazides Loop diuretics Other causes ``` Hypertension Hyperlipidaemia

Answer 18

Features of ankylosing spondylitis back pain Prolonged morning stiffness. Improved with Movement. Alternating buttock pain. Features of bone metastasis / myeloma back pain History of cancer. Systemic cancer symptoms eg. fever / weight loss / night sweats. Features of discitis back pain Systemic infection symptoms eg. fever / weight loss / night sweats. Immunosuppression. IV drug usage. Features of vertebral fracture back pain Violent trauma. Features of cauda equina syndrome / spinal cord compression back pain New urinary or faecal retention or incontinence Poor anal tone or reduced perineal sensation (saddle anaesthesia) Bilateral lower limb neurology (alternating or simultaneous) ``` Features of nerve root compression back pain Normally unilateral (unless there is bilateral disease) ``` Burning/shooting pain down the leg Positive sciatic stretch test Dermatomal stretch test positive Reduced reflexes Cancers that metastasise to the bone Cancers that commonly metastasise to the bone can be remembered with the mnemonic BLT with a Kosher Pickle: ``` Breast Lung Thyroid Kidney Prostate. ```

Answer 19

GBS is an ascending inflammatory demyelinating polyneuropathy. Causes Typically 1-3 weeks after infection (e.g. Campylobacter, mycoplasma, EBV). 40% of cases are idiopathic. Clinical features Progressive ascending symmetrical limb weakness (affecting the lower limbs first). Paraesthesiae may precede the onset of motor symptoms. Respiratory muscles may be affected in severe cases. Some cases present with symptoms of cranial nerve palsies (e.g. diplopia, facial droop). Lower motor neurone signs in the lower limbs (hypotonia, flaccid paralysis, areflexia). Cranial nerve signs may also be present (e.g. ophthalmoplegia, lower motor neurone facial nerve palsy, bulbar palsy) as well as signs of type 2 respiratory failure due to respiratory muscle weakness (e.g. CO2 flap, bounding pulse). Autonomic dysfunction may be present (e.g. arrhythmia, labile blood pressure). Investigations Bedside tests include spirometry (checking for a reduced FVC). Bloods include an ABG (to check for type 2 respiratory failure) and anti-ganglioside antibodies. Other investigations include a lumbar puncture which typically shows a raised protein, with normal cell counts and glucose (so called albuminocytological dissociation). Management Conservative measures include monitoring of ventilation (with serial spirometry and ABG) ± ventilation, measures to reduce the risk of VTE (TEDs, LMWH), and protection of pressure areas. Medical management is with intravenous immunoglobulin and, if ineffective, plasmapheresis. Note that Miller-Fisher syndrome (a variant of GBS) presents with ataxia, ophthalmoplegia, and areflexia. The condition is typically positive for anti-GQ1b antibodies.

Answer 20

rescbyacusis Prescbyacusis describes age-related hearing loss. Her young age makes this diagnosis unlikely. Additionally, presbyacusis describes a sensorineural hearing loss, which would be worse with background noise, not better. 6% Otosclerosis This patient has risk factors for otosclerosis: onset in early adulthood, exacerbated by pregnancy. Otosclerosis is usually bilateral and causes a conductive deafness (better with background noise). It is frequently associated with tinnitus (high pitched ringing noise). The otoscopy image clinches the diagnosis - this patient has a pink tinge to the tympanic membrane, which is known as Schwarze sign or Flamingo flush, which only occurs in 10% otosclerosis cases but is highly specific. 64% Vestibular schwannoma This is more likely to cause a sensorineural hearing loss (worse in background noise) than conductive. It very rarely occurs bilaterally. Indeed, bilateral schwannoma should prompt consideration of a genetic syndrome e.g. neurofibromatosis. It is not associated with pregnancy. Otosclerosis is the most common cause of progressive deafness in young adults.

Answer 21

Inheritance It is an autosomal dominant condition and the majority of patients have significant family histories. Pathophysiology In otosclerosis, the bone around the base of the stapes becomes thickened and eventually fuses with the bone of the cochlea. This prevents the stapes natural function as a piston onto the cochlea and conduction progressively gets worse until a maximal conductive hearing loss of 60dB is reached. Management Initial treatment for otosclerosis may involve hearing amplification through hearing aids or surgical replacement of the stapes bone through a stapedectomy

Answer 22

Nephrotic syndrome is a clinical syndrome that arises secondary to increased permeability of serum protein through a damaged basement membrane in the renal glomerulus. Clinical Features It is typically characterised by a proteinuria (>3-3.5g/day), oedema, hypoalbuminaemia and hyperlipidaemia and lipiduria. Pathophysiology Cytokines damage podocytes causing them to fuse together and destroy charge of the glomerular basement membrane. This allows increased permeability to plasma proteins. This causes massive protein loss in the urine. As a result of this, serum albumin levels are reduced beyond the synthetic ability of the liver. Thus patients experience marked oedema as with less albumin in the blood stream, there is less oncotic pressure. This lets fluid leak out into the interstitium. As an attempt to maintain oncotic pressure, the liver tries to compensate by increased synthesis of lipoproteins, this is one of the mechanisms postulated to cause the hyperlipidaemia. However, the full mechanism is not fully understood. Causes The most common cause in adults is membraneous glomerulonephritis. The most common cause in children is minimal change disease. Systemic Disease Diabetes Mellitus (Glomerulosclerosis) Systemic Lupus Erythematosus (Membranous) Amyloidosis Minimal Change Glomerulonephritis Associated with upper respiratory tract infection Biospy: normal light microscopy, fusion of podocytes on electron microscope Treat with steroids 1% go on to have end-stage renal failure Membranous nephropathy Associated with cancers (Lung, Colon Breast), infections (SLE, thyroid disease), infections (Hepatitis B) and drugs (Penicillamine and Gold) Biopsy: subepithelial immune complex deposits 40% have spontaneous remission Focal segmental glomerulosclerosis More common in Afro-caribbean population Associated with Berger's disease, sickle cell, HIV Biopsy: focal scarring, IgM deposition Treat with steroids or cylophosphamide/ciclosporin 30-50% progress to end stage renal failure Membranoproliferative/Mesangiocapillary Less common May present as both nephrotic or nephritic Associated with Hepatitis B, Hepatitis C and Endocarditis 50% progress to End-Stage Renal Failure Clinical Presentation Periorbital and peripheral oedema. Investigations Bedside investigation include urine dipstick which reveals proteinuria. Urine analysis reveals a raised albumin creatinine ratio. Renal biopsy is indicated in all adults but should only be done in children with an atypical presentation (e.g. steroid unresponsive, haematuria, under 1 years old or over 12 years old). Management High dose steroids which should be tapered according to clinical response. Complications Infection (due to urinary loss of immunoglobulins) Venous thromboembolism (due to urinary loss of antithrombin III) Hyperlipidaemia (due to increased hepatic production of lipids to restore the serum oncotic pressure) Prescribe a long-course of Prednisolone This is the correct answer. This patient has presented with clinical features of nephrotic syndrome including significant peripheral oedema and massive proteinuria. This is due to minimal change glomerulonephritis, the most common cause of nephrotic syndrome in children. The disease is caused by effacement of glomerular podocyte processes, which can only be detected using high resolution electron microscopy. No glomerular abnormalities are typically visualised using light microscopy, giving the disease its name. The definitive management of minimal change glomerulonephritis at initial presentation is with a 12-week course of Prednisolone. Albumin infusion, fluid restriction and advise low salt diet Fluid restriction and a low salt diet are conservative measures in the management of nephrotic syndrome, but would not be effective at addressing minimal change glomerulonephritis, which is the underlying cause for this patient's presentation. An Albumin infusion would be appropriate in patients with nephrotic syndrome who present with significant respiratory distress, haemodynamic instability, and significant oedema. However, this patient's observations are stable.

Answer 23

Tuberculosis (TB) is a chronic granulomatous disease caused by Mycobacterium tuberculosis. Transmission Tuberculosis is transmitted by inhalation of droplets infected with Mycobacterium tuberculosis. These droplets are produced by infected patients when they cough, and infective organisms can survive for long periods of time in the environment. Epidemiology 1/3 of the global population has latent TB infection More than 95% of deaths due to TB occur in low and middle-income countries, where it is a leading cause of more mortality 1/5 of all HIV deaths are due to TB. The incidence of TB in the UK is high compared to other Western countries (13.9/100000 in 2012). Clinical Features Primary and secondary infection: In 90% the immune system contains the infection, through macrophages that engulf bacteria and localize them to the hilar lymph nodes. Here, they are eliminated or may be encapsulated by a barrier of granulation tissue (considered to be in a dormant state). A small proportion progress to active TB, with an increased risk in those who are immunosuppressed (e.g. HIV). This is known as Secondary TB and usually occurs in the apex of the lungs. From here it can spread locally or to distant sites. Some patients are not able to contain the primary infection, and it disseminates widely via the bloodstream. This is known as miliary TB (due to the characteristic pattern on Chest X-ray like 'millet-seeds' when re-infection of lungs occurs after passing through circulation). Risk Factors Ethnic minority groups (most commonly those from sub-Saharan Africa and South Asia). The risk is highest if returned from a high-prevalence country in the last 5 years. The homeless - associated with overcrowding, poor living conditions and malnutrition. Drug and alcohol abuse - associated with overcrowding, poor living conditions, and malnutrition. Close contact with infected patient: household members have a 1/3 risk of infection. However, healthcare workers, and contacts at school or work are also at particular risk. Immunosuppression: result in reactivation of latent disease or primary miliary infection. Conditions include HIV, chronic organ failure, Diabetes Mellitus, chronic malnutrition. Young or old age: due to immature immune systems in the very young. General Presentation Subacute to chronic in onset Symptoms depend on the main site of infection, but are usually accompanied by; night sweats fever weight loss other systemic symptoms Pulmonary Presentation Most common Chronic cough productive of purulent sputum +/- hemoptysis. Can get bronchiectasis, pneumonia and pleural effusions. CNS Presentation TB meningitis or tuberculoma Headache Meningism Focal neurological signs Decreased consciousness Genitourinary Presentation Second most affected organ system outside of the lungs. Causes 'sterile' pyuria, kidney pathology, abscesses, salpingitis and infertility, epididymo-orchitis. Musculoskeletal Presentation Arthritis Osteomyelitis Psoas abscess Pott's Disease of the Spine. Gastrointestinal Presentation Abdo pain Obstruction, appendicitis due to ileocaecal lesions. Can get spread to peritoneum causing ascites. Pericardial Presentation Pericardial effusions Constrictive pericarditis (usually see calcification of the pericardium on imaging) Lymph Nodes May get palpable tender, firm superficial lymphadenopathy. These can later become suppurative (known as scrofuloderma) Cutaneous Presentation A wide range of skin reactions including erythema nodosum and Bazin's disease. Investigations Chest X-ray Sputum samples for culture and sensitivity testing (at least three needed - may need to consider lavage or sputum induction if cannot produce) Samples from non-pulmonary sites: may need biopsy and needle aspiration Samples are stained with Ziehl-Neelsen or Auramine staining for direct microscopy For culture, Lowenstein-Jensen (LJ) media is needed. PCR - GeneXpert, rapid results with additional drug sensitivity tested as well. Interferon-Gamma Release Assays (IGRAs) - cannot tell difference between latent or active TB, and not useful in very young or immunosuppressed patients. Results are obtained rapidly, however, and are not affected by prior BCG. Mantoux test - usually offered to contacts of infected patients. Positive in those who have had the BCG vaccine. Management Isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months, then Isoniazid and rifampicin for a further 6 months. Extended duration in TB meningitis, pericarditis, and spinal TB. Side effects of Isoniazid Peripheral neuropathy (pyridoxine is given to prevent this) Liver toxicity Side effects of Rifampicin Liver toxicity Hepatic enzyme (p450) inducer Turns bodily fluids red/orange color. Side effects of Ethambutol Visual disturbance (color blindness, loss of acuity etc.) Avoid in chronic kidney disease. Side effects of Pyrazinamide Liver toxicity Second line treatments Note that MDR-TB and extensively drug-resistant TB are increasing in global incidence, particularly in South Africa, Eastern Europe, and Asia. Second-line drugs for MDR-TB include amikacin, macrolides, quinolones, and capreomycin. Extensively drug-resistant TB is very difficult to treat, particularly in low-resource countries. Start initial phase quadruple antibiotic therapy immediately It is important to start therapy without delay when signs and symptoms point to a diagnosis of acute pulmonary TB. According to both British Thoracic Society and NICE guidelines, you can start treatment without waiting for the results of the sputum culture (which you would ideally ask the patient to produce prior to starting therapy). The classic quadruple therapy regimen includes Isoniazid, Rifampicin, Ethambutol and Pyrazinamide.

Answer 24

Vertigo is a hallucination of movement of oneself or one's surroundings. This movement is often rotatory; for example, one may feel as though the floor is tilting. Causes of vertigo There are several causes of vertigo: Benign positional paroxysmal vertigo (BPPV) features The presence of debris in the semicircular canals of the ears causes vertigo upon head movement. The Hallpike manoeuvre is diagnostic, where certain movements of the head causes fatiguable nystagmus. Epley manoeuvres treat BPPV by clearing the debris. Acute labyrinthitis features Inflammation of the vestibular nerve causes an acute severe vertigo, which may be associated with vomiting. The term 'vestibular neuritis' is sometimes used interchangeably but should be confined to cases where only the vestibular nerve is involved. In practice, acute labrynthitis and vestibular neuritis can be distinguished by the presence and absence of hearing dysfunction. Therefore, acute labrynthitis can present with hearing loss and tinnitus, whereas vestibular neuritis does not. It is often associated with a recent viral illness or a vascular lesion, in which case it may involve other cranial nerve deficits. It often resolves completely over a month, so treatment is conservative, although sedatives may help in severe cases. Ménière's disease features Endolymphatic system pressure increases causes recurrent episodes of vertigo, sensorineural hearing loss, tinnitus, and a feeling of aural fullness. Treatment involves antihistamines and bed rest. Acoustic neuroma features Actually a vestibular schwannoma. They usually present with unilateral hearing loss and progress to involve cranial nerves 5, 6, 9, 10, and the ipsilateral cerebellum. Ramsay Hunt syndrome features Herpetic infection of the facial nerve causes a facial nerve palsy, with or without vertigo, tinnitus, and hearing loss. This is treated with aciclovir and prednisolone. Ototoxicity features Caused by aminoglycoside antibiotics (eg. gentamicin, vancomycin) and loop diuretics (eg. furosemide), most commonly

Answer 25

Obstructive sleep apnoea is caused by intermittent closure and collapse of the upper airway leading to apnoeic episodes during sleep. Presentation Excessive daytime sleepiness Lack of concentration Snoring Unrefreshing sleep Irritability/personality change Risk factors Obesity Male Smoking Alcohol excess Micrognathia Neuromuscular disease Investigations Polysomnography is the traditional gold standard investigation. Physiological parameters are measured while the patient is asleep overnight Blood pressure Management Weight loss Smoking cessation Alcohol avoidance in the evening (sedative effect) CPAP (Continuous positive airway pressure) maintains upper airway patency and is the gold standard Complications Accidents related to excessive daytime sleepiness Cardiovascular complications such as hypertension Psychological consequences Association with other cardiovascular comorbidities such as coronary artery disease, myocardial infarction, stroke and type 2 diabetes Associated with increase in all cause mortality

Pathology 8 Flashcards

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