PACES Viva Questions Flashcards
List some reasons for performing a pneumonectomy or lobectomy
- Lung malignancy (Common) and Pulmonary Metastasis (Rare)
- Localised bronciectasis with uncontrolled symptoms e.g. recurrent Haemoptysis
- Old TB (Prior to anti-TB meds)
- Fungal infections e.g. aspergilloma
- Traumatic lung injury
- Large emphysematous Bullaea (Bullectomy)
- Congenital lung disease e.g. Cystic fibrosis
- Bronchial obstruction with destroyed lung.
What are the chest radiograph is features in a pneumonectomy /Lobectomy?
On PA CXR the following features will be seen:
- White out on one side (Pneumonectomy)
- In lobectomy there may be volume loss in the ipsilateral hemithorax, increased transradiancy of the ipsilateral lung due to compensatory hyperinflation, the presence of surgical clips and evidence of rib resections.
- Deviated trachea or mediastinum towards the pneumonectomy or lobectomy
- Compensatory hyperinflation of contralateral lung in pneumonectomy.
What is the importance of preoperative evaluation on pneumonectomy?
Preoperative evaluation is vital in both pneumonectomy and lobectomy because of the significant loss of lung function that follows.
Additionally, because such interventions are usually performed in patients with underlying lung disease, it is essential to assess the patients functional reserve and predicted pulmonary function follow surgery.
Pre-operative FEV1 over 2L is associated with low risk, no further testing required in absence of pulmonary hypertension (1.5L is acceptable for patients undergoing lobectomy)
Pre-operative FEV1 less than 2L is high risk, these patients require predicted post operative FEV1 and Gas transfer estimations following quantitative lung ventilation / perfusion scanning.
Preoperative cardiopulmonary tasting can also be performed. A Pre Operative VO2 Max less than 10mL/Kg/Min is associated with a high mortality risk (over 30%) versus those with preoperative VO2 Max over 15mL/Kg/min which are associated with a Mortality Risk less than 15%
Are you aware of any subtypes of pneumonectomy?
There are 2 main types of pneumonectomy:
- simple - removal of affected lung
- Extrapleural - removal of affected lung plus part of the diaphragm, parietal pleura, and pericardium on ipsilateral side. These are then replaced by surgical Gore-Tex
The primary use of extrapleural pneumonectomy is in the treatment of malignant mesothelioma because this particular technique has been shown to have the best survival rates. (Clinical oncology study 2008)
If this patient had a lobectomy secondary to lung malignancy, can you suggest a likely subtype of lung cancer?
Surgery has a greater role in the management of ‘NSCLC’ rather than Small cell Carcinoma the latter of which has a poorer prognosis and is almost always unsuitable for surgical intervention by the time of presentation.
The most common type of NSCLC is squamous, followed by Adenocarcinoma, alveolar cell, large cell, carcinoid.
What proportion of NSCLC are suitable for surgery?
Approximately 25% of NSCLC will be suitable for surgical resection
Comment on the operative mortality or (i) Lobectomy and (ii) Pneumonectomy? Are there any differences between the right and left sides?
Operative mortality for lobectomy is approximately 2-4% and for pneumonectomy this rises to 6%.
There is a marked difference is mortality rates between the right and left sides following pneumonectomy. Right sided pneumonectomy is associated with higher overall mortality (10-12%) as compared to left-sided (1-3.5%). Reasons are uncertain for this difference but are most-likely due to life threatening complications that are encountered at a higher frequency following right-sided procedures such as post-pneumonectomy space empyema, pulmonary oedema, and bronchopleural fistula.
What is the ‘Post-Pneumonectomy syndrome’?
This syndrome results from the extrinsic compression of the distal trachea and main-stem bronchus due to mediastinal shifting and compensatory hyperinflation that occurs in the remaining lung.
Post-pneumonectomy syndrome occurs almost exclusively in patients with right sided pneumonectomy , approximately 6 months post surgery but can occurs years after the procedure.
The syndrome is characterised by progressive dyspnoea, cough, inspiratory stridor, and pneumonia. Treatment includes surgical repositioning of the mediastinum and filling fo the post-pneumonectomy space with non-absorbable material +/- stenting of the bronchi.
This condition can be fatal if not treated.
What are the indications for VATS procedure?
Lobectomy and pneumonectomy
Correction of spontaneous primary pneumothorax
Wedge resection
Lung parenchymal biopsy
Bullectomy and lung volume reductions surgery
What are the main differences in approach in VATS vs Open Thoracotomy?
VATS is associated with better cosmetic outcomes utilising smaller incisions, reduced in hospital recovery and total recovery. Less discomfort.
However it is associated with an increased risk of recurrent pneumothorax 5% vs 1% in Open thoracotomy.
Describe the Risk factors for developing Lung Cancer
Smoking - estimated 90% of all lung cancers caused by smoking. Adenocarcinoma is the only subtype not associated with smoking. Current smoker of 40 Pack years has a 20-fold increase risk.
Radiation therapy
Environmental exposure to passive smoke, asbestos, radon, metals (Arsenic, Chromium, Nickel)
Pulmonary fibrosis
COPD
Alpha 1 Antitrpsin deficiency,
Genetic factors i.e increased risk in those with family history.
Describe the histological classification of lung cancer.
Non-Small Cell Lung Cancer (NSCLC)
- 75%-80% of lung cancer
- Squamous, adenocarcinoma, alveolar, large cell
Small Cell Lung Cancer
- 20-25% of lung cancer
- rapidly proliferating tumour with early dissemination.
Name the common sites of Lung metastases.
Liver
Adrenal Glands
Bone - Osteolytic appearance, most commonly in vertebral bodies
Brain
What are the most common paraneoplastic syndromes that affect lung cancer patients?
Hypercalcaemia
SIADH
Describe the staging classification of NSCLC
Classified using TNM classification:
T1 tumour less than 3cm
T2 tumour greater than 3cm or involves main bronchus, or more than 2cm distal to the carina, or invading visceral pleura.
T3 tumour of any size that invades the chest wall, diaphragm, mediastinal pleura, parietal pericardium or tumour in main bronchus less than 2cm distal to the carina.
T4 tumour of any size that invades the mediastinum, heart, great vessels. Trachea, oesophagus. Or a tumour with malignant pleural/pericardial effusion or a tumour with satellite lung nodules within the same lobe as the primary.
N0 - No regional lymph nodes
N1 metastasis to ipsilateral peribronchial or hilar lymph nodes
N2 metastasis to ipsilateral mediastinal or subcarinal nodes
N3 metastasis to contralateral nodes or ipsilateral scalene or supracalvicular nodes.
M0 No distant Metastasis
M1 Distant metastases
Describe the classification of SCLC
Limited disease:
- Disease confined to ipsilateral hemithorax
- Median range survival 15-20 months
Extensive Disease:
- Metastatic Disease outside ipsilateral hemithorax
- Median range of survival 8-13 months
What other prognostic factors help guide treatment in lung cancer?
WHO Performance Score:
- 0 Asymptomatic
- 1 symptomatic but ambulatory and able to carry out light work
- 2 in bed less than 50% of the day
- 3 in bed over 50% of the day and unable to self care
- 4 bed bound
Weight Los
Describe the management of patients with NSCLC
Patients should be discussed at a lung cancer MDT meeting and given information regarding their diagnosis and treatment. Lung cancer nurse specialists are essential to provide continuing support or the patient and coordinate their care.
Surgery:
- Surgical resection in the form of lobectomy or pneumonectomy offers the best long-term survival for patients with lung cancer
- Considered in patients with stage I and II disease and considered on an individual basis in patients with Stage IIIa disease.
- Patients need to be careful selected based on adequate lung function and co-morbidities.
- Classically patient with an FEV1 greater than 2L (or 80% predicted) can tolerate pneumonectomy and FEV1 greater than 1.5L patient can tolerate Lobectomy. Patients with a DLCO over 80% have low postoperative risk.
- Patients who do not clearly fit a low-risk category can have further testing to assess their predictive postoperative lung function, taking into account preoperative lung function, amount of tissue to be resected and preoperative contribution of tissue to be resected to overall lung function. A Predicted postoperative FEV1 of over 40% normal predicted is required for surgery.
- Cardiopulmonary exercise testing is performed to assess the level of work a patient can achieve, measured by maximal oxygen consumption VO2 Max. VO2 Max less than 10mL/Kg/Min is associated with increased risk (30% mortality) whereas VO2 max over 15mL/Kg/Min is deemed acceptable (Less than 15% mortality)
- Postoperative adjuvant chemotherapy has been shown to improve survival with patients with Stage II disease.
Radical Radiotherapy:
-CHART (Continuous hyperfractionated accelerated radiotherapy) is considered in patients with Stage I, II, III disease who are inoperable but have good performance status
Chemotherapy:
- Offered to patients with III or IV cancer with good performance status. (WHO 0-1)
- Usually a platinum-based drug (Carboplatin, Cisplatin) combined with a 3rd generation drug (Docetaxel, gemcitabine, paclitaxel, or vinorelbine)
- COmbination of chemotherapy and radiotherapy provides a survival advantage in patients with stage III disease.
Palliative Treatment:
- Stage IV Disease
- Radiotherapy to control symptoms
- Chemotherapy in patients with good performance status can prolong survival without significant impairment of quality of life.
- symptoms control wit analgesics, anti-emetics, steroids (may improve appetite and performance status)
- planning end of life care wit the support of the palliative care team.
Describe the management of small cell lung cancer
Combination treatment with radiotherapy and platinum-based chemotherapy
Prophylactic cranial irradiation considered in patients who respond to treatment - shown to reduce the incidence of brain metastases (Common after treatment for SCLC due to inadequate penetration of chemotherapy agents through the blood-brain barrier) and prolong survival
What treatment are available to help patients stop smoking?
Smoking cessation improves symptoms, improves lung function (there is a significantly reduced rate of decline in FEV1 with a return to near normal age-related decline over time) and is the only treatment sown to alter disease course.
Behavioural Treatment:
- 5 A approach endorsed by the BTS, Ask about smoking status, Assess readiness to quit, Advise to quit, Assist in efforts to quit, Arrange follow-up.
- Patients should be encourage to identify a quit day.
- Informing patients of abnormal lung function increases their likelihood of quitting
- Group-counselling includes lectures, habit recognition, copying skills and suggestions for relapse prevention.
Nicotine Replacement Therapy:
- Insufficent evidence to conclude one form of NRT is more effective than another.
- Nicotine patches, gum, inhalers (Can cause bronchospasm), nasal sprays (REsults in more rapid rise in plasma nicotine levels mimicking smoking, can cause nasal irritation)
Buproprion:
-Antidepressant which enhances CNS noradrenergic and dopaminergic function.
Varenicline:
-Partial agonist of nicotinic acetylcholine receptors, Side-effects include abnormal dreams, nausea and neuropsychiatric symptoms.
Some evidence of increased efficacy with combination treatment. No evidence for the effectiveness of acupuncture or hypnosis.
Describe the treatment options available for COPD
Non-Pharmacological Treatment:
- Pulmonary rehabilitation, multidisciplinary programme of care incorporating disease education, physical training, nutritional, psychological and behaviour interventions. Leads to a statistically significant improvement in exercise capacity and quality of life and reduces dyspnoea with conflicting evidence regarding effect in reducing hospital admissions. Consider in patients with MRC Dyspnoea Grade 3+
- Optimize nutrition, poor nutritional states associated with increased mortality, impaired respiratory muscle function and reduced immune function
- Vaccinations, infleunza should be offered to all patients and pneumococcal in patients over 65 of with an FEV1 less than 40% predicted.
Pharmcological Treatment:
- Treatment aims to reduce symptoms, decrease frequency and severity of exacerbation, improve quality of life and increase exercise capacity. Medication can be relieved by pressurised metered dose inhaler, dry powder inhaler with or without spacer or nebulisers. Inhalers can achieve response equivalent to nebulisers if used correctly an inhaler technique should be checked regularly.
- Short acting bronchodilators, short acting beta 2 agonists act directly on bronchial smooth muscle to cause bronchodilation e.g. salbutamol terbutaline.
- Short acting anticholinergics inhibit resting bronchomotor tone and affect muscular secretion e.g. Ipratropium bromide.
- combination treatment has additive effect. Does not alter the frequency of exacerbations.
- Long-acting bronchodilators: recommended in patients who remain symptomatic on above treatment of experience more then 2 exacerbations a year.
- Long acting beta 2 again it’s : TORCH STUDY (TOwards a Revolution in COPD Health) - salmeterol reduced exacerbation rates, improved lung function and health-related unlit you of life compared to placebo.
- Long-acting anticholinergics: UPLIFT study (Understanding the Potential Long-term Impact on Function with Tiotropium) treatment with tiotropium therapy (Versus placebo in patients permitted to use other respiratory medications except anticholingergics) shown to improve lung fun UTI mood reduce exacerbation and improve health-elated quality life over a 4 year period.
Inhaled Corticosteroids:
- Reduce airway and systemic inflammation. Indicated for patients with an FEV1 Less than 50% predicted who are having more than 2 exacerbation a year. 12 RCTs demonstrated reduction in risk of exacerbation versus placebo with no significant effect on mortality. TORCH study fluticasone propionate reduced rate of moderate severe exacerbation and improved quality of life and improved lung function vs placebo.
- Frequency of pneumonia increase in patients use ICS and increased risk of oral candies is but this did not have a significant effect on mortality.
Oral Corticosteroids:
-Associated with increased morbidity and mortality and therefore use of oral cortical steroids is not recommend. Trial of oral corticosteroids does not predict response to inhaled treatment.
Combination treatment LABA + ICS:
-TORCH Study showed salmteraol and fluticasone combined improved lung unction, health status and frequency exacerbation compared to individual therapies and placebo. Mortality reduced compared to placebo but had borderline significance. Further analysis has showed therapy to slow rate of lung function decline.
Theophylline:
- Unclear mechanism of action, relaxes airway smooth muscles. May improve diaphragm strength and affect mucociliary clearance.
- Given potential toxicity and drug interaction and need to monitor plasma levels it is no recommended for initial treatment.
Oxygen:
- LTOT is indicated in patients with PaO2 less than 7.3kPa, or less than 8kPa in the presence of secondary polycythaemia, nocturnal hypoxaemia, cor pulmonale or pulmonary hyfunction hypertension. Needs to use more than 15hours a day and improves survival and quality of life.
- AMbulatory oxygen is considered in patients who desaturate on exercise of show improvement in exercise capacity with oxygen.
- Short-burst oxygen is on spider in patients with epsiodes of severe breathlessness not relieved by alternative treatments
Non-Invasive Ventilation:
- Considered in patients with CHronic II respiratory failure despite adequate treatment.
- May rest fatigued respiratory muscles, improve sleep quality and by reducing nocturnal hypoventilation, may reset respiratory centre leading to improvements in daytime hypercapnia
Describe the role of surgery in patients with COPD
Lung Volume reduction surgery:
- Removing areas of poorly functioning lung (and thus allowing expansion of more physiologically useful lung) can improve exercise capacity, quality of life and mortality in a select group of patients
- Patients who remain symptomatic despite maximal medical therapy and pulmonary rehabilitations and have FEV1 over 20% predicted, PaCO2 less than 7.3kPa, TLCO over 20% predicted and predominantly upper lobe emphysema should be referred for consideration
Bullectomy:
- Bullectomy improves symptoms and lung function by reducing airway resistance and functional residual capacity, improving elastic recoil, restoring the mechanical linkage between the chest wall and normal lung and moving the diaphragm into more efficient position.
- Should be considered in patients with progressive dyspnoea despite maximal medical treatement, FEV1 less than 50% predicted and bullae over 1/3 hemithorax with preserved function in surrounding lung.
Lung Transplant:
- can improve functional capacity
- The international Society for Heart and Lung Transplant registry report an overall 1 year survival of 78% and 5 year survival of 51%. However the true increase in survival over the natural history of COPD is less clear
- Guidelines for referral include: BODE index > 5, post bronchodilator FEV1 less than 25%, resting hypoxaemia and hypercapnia, secondary pulmonary hypertension and accelerated decline in FEV1.
What causes an acute exacerbation of COPD?
Infection (60%):
- Viruses: Rhinovirus, influenza, parainfluenza, cornavirus, adenovirus
- Bacteria: haemophilus influenza, Moraxella catarrhalis, streptococcus pneumonia, pseudomonas, enterobacteria, Incidence of atypical is low
Environmental pollution (10%)
Unknown Aetiology (30%)
How are infective exacerbations of COPD treated?
- Controlled oxygen therapy to achieve arterial oxygen saturation’s of 88-92%
- nebulised beta-2-agonists
- nebulised anticholinergics
- oral corticosteroids: improve lung function and reduce hospital length of stay
- antibiotics: initial empirical treatment with amino penicillin, macrolides or tetracycline.
- Aminopylline: not recommend as first line treatment, RCT have failed to show benefit compared to effect of bronchodilators and steroids. Significant side-effects including nausea, tremor and tachyarrhythmia
- Discharge planning should involve a community COPD treatment team.
Describe the use of non-invasive ventilation (NIV) in the treatment of acute exacerbations of COPD.
Bi-level positive airway pressure (BiPAP) provides pressure support via a facemask with higher inspiratory positive airway pressure (IPAP) than expiratory positive airway pressure (EPAP)
- Ventilators differ in delivering either a selected volume or pressure and can be timed or patient-triggered, with back-up rates if the patient fails to breathe.
- NIV improves oxygenation, increases the removal of CO2, increases functional residual capacity, increases tidal volume, improves lung and chest wall mechanics and decreases respiratory effort.
Compared to conventional medical care NIV has been shown to:
- Decrease the need for endotracheal intubation
- improve pH and respiratory rate
- Result in fewer complications (principally ventilator associated pneumonias)
- Result in shorter lengths of hospital stay
- Reduce mortality
Indications:
- NIV should be considered in patients who despite maximal medical treatment and controlled oxygen therapy have a respiratory acidosis (pH less than 7.35)
- patients should be able to consent to treatment and have potential for recovery to a quality of life that is acceptable to the patient.
- relative exlusion criteria include: life-threatening hypoxaemia, severe comorbidity, confusion, facial injuries, vomiting, fixed upper airway obstruction, inability to protect airway, undrained pneumothorax, haemodynamic instability, bowel obstruction or upper gastrointestinal surgery.
- in patients in whom endotracheal intubation is inappropriate there is flexibility for these guidelines, for example an unconscious patient secondary to COPD induced hypercapnia.
Commencing NIV:
- At the time of commencing NIV a decision regarding the most appropriate ceiling of care for the patient should be documented (e.g. should they be intubated and mechanically ventilated if NIV fails) and a resuscitation decision should be made.
- Initial pressures recommended are 12-16cmH2O and EPAP 4-5cmH2O with oxygen adjusted to reach target saturation’s 88-92%. Pressures are adjusted depending on patient tolerability and clinical response. Patients should be closely monitored with repeat blood gases 1 hour after commencing of NIV or following change in settings.
How does CPAP (Continious positive airway pressure)differ from non-invasive ventilation?
- CPAP maintains these same pressure support throughout the breathing cycle, splinting open the upper airways, recruiting collapsed alveoli (Thus improving lung compliance) and reducing ventilation/perfusion mismatching.
- It is used for the treatment of acute pulmonary oedema, obstructive sleep apnoea and Type 1 respiratory failure.
What is Hamman-Rich syndrome?
It is an acute, rapidly progressive lung fibrosis also known as acute interstitial pneumonia (AIP). It may respond to steroids but has a poor overall outcome (6-month survival 22%)
What different Types of Computed Tomography (CT) imaging do you know about and when should each be used?
There are 3 main types of CT Scanning:
High-resolution Computed tomography (HRCT: 1-1.5mSv):
- involves taking very thin sections (1mm) with high spatial frequency re-constructions with ‘skipped’ areas between the thin sections (1mm every 10mm therefore produces sampling of the lung but not continuous imaging)
- Images obtained in inspiration and expiration and additionally whilst supine and prone(to exclude dependant change seen on scans which can be mistaken for pathology/disease)
- Most useful for assessment of interstitial processes such as fibrosis or emphysema and endbronical changes with ‘Tree in bud’ appearances.
Dynamic (Standard CT:8mSv):
- involves taking thicker sections (10mm) which are then used for reconstruction (Provides continuous images in contrast to HRCT).
- intravenous contrast may be used as it clarifies anatomy and boundaries of the great vessels and improves assessment of the mediastinum and hilar regions for lymphadenopathy.
- most useful or assessment of airspace disease (pneumonia or malignancy) and mediastinal pathology (Lymph nodes in staging)
Computed Tomography pulmonary angiogram (CTPA: 8mSv):
- involves very thin sections (Can be variable e.g. 0.5-0.625mm) in a continuous fashion to obtain images of the pulmonary arteries using multi-detector CT scanning (MDCT)
- Main diagnostic investigations to detect pulmonary embolism.
What are the main treatments available for ‘pulmonary fibrosis’?
Treatments options include the following:
- Corticosteroids (factors contributing to lack of response include male sex, severity of symptoms or worse lung function on presentation, neutrophilia on BAL or predominant honeycombing on CT)
- Immumnosuppresives (Cyclophosphamide, azathioprine, methotrexate, and cyclosporine)
- Anti-oxidant (N-acetylcysteine in conjunction with corticosteroids and Azathioprine)
- Supplemental Oxygen (PaO2 less than 7.3kPa or 8kPa with cor pulmonale)
- Lung transplantation (60% 1 year survival)
In addition to glucocorticoids and immunosuppressives, are you aware of any other potential treatments for Pulmonary Fibrosis?
Agents acting as anti-fibrotic have been suggested for use in the management of pulmonary fibrosis. Evidence for their use is limited and therefore they are rarely used in clinical practise e.g. pirfenidone. Other drugs that may be of use include bosentan and warfarin due to their role in pulmonary hypertension.
Comment on prognosis and list favourable prognostic factors in idiopathic pulmonary fibrosis (IPF)
The median survival is 2.8 years. 5-year survival 50% (60% in steroid responders and 25% in non-responders). Favourable prognostic factors include the NSIP subtype.
Which disorders typically have a high lymphocyte count on BAL?
Hypersensitivity Pneumonitis
Sarcoidosis
Organising pneumonia
Lymphocytic interstitial pneumonia (LIP)
Describe the possible respiratory manifestations in rheumatoid arthritis (The rheumatoid Lung)
There are 5 main respiratory manifestations of rheumatoid arthritis. It is however to important to note that nowadays rheumatoid arthritis related lung disease is seen much less frequently due to earlier and more aggressive treatment regimes:
Pleural effusions:
- males more than females
- Usually asymptomatic; respiratory symptoms will only occur if effusion large enough
- Characteristically low glucose and rheumatoid factor +Ve effusions.
Pulmonary nodules:
- May be seen on radiography and precede arthritis onset.
- usually asymptomatic but may become infected, cavitation, or cause haemoptysis.
- predilection for upper lobe location
Fibrotic lung disease:
- 2% of all cases become symptomatic, however subclinical disease is common with a reduced DLCO on PFTs and UIP pattern on HRCT.
- Can result directly from disease or secondary to treatment (Methotrexate/gold). If secondary to treatment, changes may regress on discontinuation of the offending drug.
Caplan Syndrome: coal worker pneumoconiosis and rheumatoid arthritis
Obliterative Bronchiolitis:
- Rare manifestation involving small airways obstruction which progress to necrotising bronchiolitis
- previously occurred in those treated with gold or penicillamine.
What scoring systems may help in the evaluation of a patient presenting with an acute alcoholic hepatitis?
Maddrey’s discriminators function test was described by Maddrey Et al in 1978 to predict prognosis in alcoholic hepatitis:
- It is calculated by 4.6 x INR + Serum Bilirubin
- during the episode a score over 32 carries a 50% mortality rate and is an indication for treatment with steroids, where as over 90% of patient less than 32 will survive.
The Mayo End stage liver disease (MELD) score has been applied to alcoholic hepatitis. This is a composite score deceived from serum bilirubin, creatinine and INR and predicts survival probability over 90 days. In one study, patients with a score less than 11 had a 30-day survival of 96% whilst the 30-day survival in those with a. Score over 11 was 45%.
The Glasgow alcoholic hepatitis score on day 1 has an overall accuracy of 81% when predicting 28-day outcome.
How would you manage a patient with acute alcoholic hepatitis?
- The mainstays of management are supportive and include: abstinence from alcohol, adequate nutrition, and treatment of any inter current infections.
- liver biopsy may be indicated to confirm diagnosis
- Maddreys Discriminant function score over 32 is an indication for treatment with steroids. 40mg oral prednisolone is frequently used. Other drugs which may be useful include pentoxifylline
What are the histological features of alcoholic liver disease?
- hepatic steatosis, accumulation of fst in liver cells, This is not related to the total alcohol exposure.
- alcoholic hepatitis, acute inflammation and hepatocyte necrosis
- hepatic cirrhosis, fibrosis of liver tissue
- while cirrhosis is irreversible and If progressive can lead to liver failure , both steatosis and hepatitis are potentially reversible following abstinence from alcohol
What clotting factor abnormalities May be associated with hepatic amyloidosis?
Hepatic amyloidosis is characteristically associated with loss of the clotting factors IX and X. In addition, infiltration with amyloid protein contributes to vascular fragility. There is significant risk of bleeding if percutaneous liver biopsy is performed and spontaneous hepatic rupture has been described
Can you name some complications of Chronic Liver Disease?
Complications of CLD include:
- Portal Hypertension
- Haemorrhage, usually GI ( gastric ulcers and erosions still occur more frequently than variceal bleeding
- Ascites
- Spontaneous Bacterial peritonitis
- hepatic encephalopathy
- hepatorenal syndrome
- hepatopulmonary syndrome
What do you understand by decompensated CLD? What are the precipitating factors which can lead to decompensated CLD?
- the liver can compensate for a significant amount of hepatocyte injury but can decompensate as a result of ongoing liver injury (continued alcohol intake or untreated chronic active viral hepatitis) or additional stress (e.g. GI bleeding, large salt intake, sepsis, constipation, dehydration)
- clinically, decompensated CLD will present with a combination of ascites, encephalopathy, hepatorenal or hepatopulmonary syndrome in an acute setting
How do you grade severity of hepatic encephalopathy?
Grade 1: Mild Confusion, euphoria or depression; Short attention span and impaired mental tasks such as addition, disordered sleep patterns
Grade 2: drowsiness, lethargy, mild disorientation mainly for time but also sometimes for place, inappropriate behaviour and personality change, impaired mental tasks such as subtraction
Grade 3: somnolent but rousable, usually with verbal stimuli sufficing. Grossly confused and disorientated , speech may be incomprehensible amnesia often present
Grade 4: comatose, no response to verbal or painful stimuli
How do you grade the severity of cirrhosis?
The most commonly used grading system for grading the severity of cirrhosis is the modified Child-Pugh system which scores clinical and biochemical parameters out of three to obtain a composite score.
Encephalopathy: none, stage 1-2, stage 3-4 Bilirubin: less than 34, 34-50, over 50 INR: less than 1.7, 1.7 -2.3, over 2.3 Ascites: None, Mild, Severe Albumin: over 35, 28-35, less than 28
Note that PSC and PBC are characterised by higher levels of bilirubin. Therefore in these conditions the criteria for bilirubin are modified to less than 68, 68-170 and over 170
Severity is classified according to the Child Pugh score into Class A (5-6) Class B (7-9) or class C (10-15) corresponding to 1-year survivals of 100%, 80%, 50% respectively.
How do you classify causes of jaundice?
Jaundice can be classified as:
- Prehepatic due to excessive breakdown of red blood cells e.g. autoimmune haemolytic anaemia, malaria, hereditary haemoglobinopathies
- hepatic due to hepatocyte injury, e.g. acute viral hepatitis, paracetamol, alcohol, hypoxic/ischaemic
- Post-hepatic due to obstruction to the normal flow of bile e.g. gallstone obstruction, pancreatic head malignancies
What do you know about hepatorenal syndrome?
Hepatorenal syndrome results from inadequate hepatic breakdown of vasoactive substances, leading to excessive vasoconstriction.
It can devolop rapidly (type 1) or slowly (type 2) and mimics pre renal renal impairment. As the kidneys attempt to conserve maximum salt and water in response to perceived hypovolaemia, the patient produces low volumes of highly concentrated (high osmolar) urine that is low in sodium.
It is usually a diagnosis of exclusion, having given a fluid challenge and ruled out obstruction, sepsis and nephrotoxic Drugs.
The kidneys of patients with hepatorenal syndrome are usually normal and in the acute setting may be salvaged. In general, if the EGFR is less than 30 in the pre-morbid state, combined liver and kidney transplantation is usually undertaken in favour of single liver engraftment as peri operative injury and postoperative immunosuppressive usually leads to loss of the remaining kidney function
How do you manage ascites in associated with CLD?
- a non salt added diet should be started ( 90mmol or 5.2g salt/day)
- spironolactone from 100-400mg/day, in all patients able to tolerate the drug without excessive hyperkalaemia
- loop diuretics should be initiated next usually furosemide from 40-160mg/day
- if these measures fail or if the patient has significant symptoms related to the ascites therapeutic paracentesis should be carried out.
- radiological procedures such as transjugular intra-hepatic portosystemic shunt procedure may help to relieve portal hypertension but the risk of encephalopathy is increased as nitrogenous waste effectively bypass the liver with a resultant increased concentration in the systemic circulation.
- surgical measures (portosystemic and peritoneovenous shunts) are much less frequently used these days but still play a role in recurrent ascites.
- liver transplantation is a curative procedure for end-stage liver disease when medical management fails
How would you investigate the cause of a sensorimotor peripheral neuropathy?
Stage 1 Investigations:
- Urine: Glucose, Protein
- Haematology: FBC, ESR, Vitamin B12 and folate levels
- Biochemistry: fasting blood glucose level;”, HbA1c, renal function, liver function, TFTs
Stage 2 Investigations:
- the most important stage 2 investigation is neurophysiological investigation. About 80% of symmetrical peripheral neuropathies are axonal.
- electrophysiological investigation (EMG and NCS) for assessment of distal and proximal nerve stimulation
- Serum electrophoresis, serum ACE
- immunology: ANA, Antiextractable nuclear antigens (Anti-Ro, Anti-La) ANCAs
- CXR
Stage 3 Investigations:
- Urine: Bence Jones Protein
- Biochemistry: oral glucose tolerance test
- CSF: Cells, Protein, Immunoglobulin oligoclonal bands
- Immunology: HIV antibodies, antineuronal antibodies ( Anti-Hu, Anti-Yo) antigliadin antibodies, antiganglioside antibodies, antimyelin associated glycoprotein antibodies
- Tests dor Sjögren’s syndrome (Schirmers rest, rose Bengal test, salivary flow rate, labial gland biopsy
- search for carcinoma, lymphoma, or solitary myeloma, skeletal survey, CTCAP, PET
- molecular genetic tests: peripheral nerve myelin protein 22 gene duplication (the commonest cause of Charcot-Marie-tooth disease type 1) or deletion (hereditary neuropathy with liability to pressure palsies) connexin 32 mutation (X Linked Charcot-Marie-Tooth disease) PO gene mutation (another cause of Charcot-Marie-Tooth disease type 1)
What is the differential diagnosis of a predominantly motor neuropathy?
These would include:
Neuromuscular junction disorders:
- Myasthenia gravis( look for complex ophthalmoplegia, ptosis, fatiguability)
- Lambert-Eaton myasthenic syndrome (associated with SCLC- Cachexia, post titanic potentiation
Distal Myopathies;
- Myotonic dystrophy (frontal balding, facial muscle wasting, cataracts, learning disability, cardiac pacemaker, percussion myotonia)
- inclusion body myositis (wasting and weakness of finger and wrist flexors (scalloping) knee extensors and ankle dorsiflexors. Weakness of the wrist and finger flexors insistem disproportionate to that of extensor counterparts. Hence loss of finger dexterity and grip strength may be a presenting or prominent feature
How may Marfan’s syndrome present acutely/ what are the acute complications?
Aortic Dissection. This is the most feared complication as the mortality is at least 50%whereas the mortality of elective aortic root replacement is 5%.
How should patients with Marfan’s be followed-up?
The major objective of follow-up is to avoid acute aortic dissection, a yearly echo should be done to monitor the aortic root, and if there is a family history of aortic dissection or the aorta has started to dilate, this should be more frequently.
What is the mode of inheritance of Marfan’s?
Autosominal dominant with complete penetrance, but very variable clinical expression. Even within a given family the manifestions can be quite variable between families there is great variation due to different mutations in the fibirillin gene. Ring present,
How is ADPKD inherited and when would you recommend screening?
ADPKD is phenotypically inherited in an autosomally dominant manner. In fact, the mutated gene is recessive to the normal allele and cysts form only in renal tubular cells where a stochastic event has lead to a mutation of the normal allele (in the same way as it the case with childhood retinoblastoma).
The usual screening test, for those who wish to have it, is an ultrasound scan of the kidneys. However as renal cysts develop with ageing, a negative ultrasound below the age of 30 does not exclude the disease.
When to screen a patient is a question of considerable debate. As there is no specific treatment for ADPKD, it can be argued that regular B checks and treatment is preferable to ultrasonic confirmation of the conditions. Others argue that the diagnosis of ADPKD should be established in everyone who is of child bearing age for the purposes of genetic counselling and for the exclusions of berry aneurysms which if sufficiently large can be treated angiograpically and reduce long term risk of subarachnoid haemorrhage.
The ultrasonic criteria for a diagnosis of ADPKD is as are as follows:
- 15-39 years of age: 3 or more cysts i the kidneys (unilaterally or bilaterally)
- 40-59 years of age: 2 or more cysts in each kidney
- over 60 years: 4 or more cysts in each kidney
Remember there are two types of ADPKD type 1 and type 2 the latter a milder phenotype.
Can you name some extrarenal manifestations of ADPKD?
Cysts in other organs Intracranial berry aneurysms Polycythaemia (Excess EPO) Hypertension (Excess Renin) Cardiac Valve disease ( Usually mitral valve prolapse but can also cause MR, TR, AR). Diverticular disease Aortic Aneurysm or thoracic coarctation Abdominal wall hernias
Can you name some organs that may contains cysts in ADPKD?
Common sites, Kidneys, Liver, Pancreases, Aracnoid cysts.
Uncommon sites: Spleen, thyroid, lungs, ovaries, testes, seminal vesicles, bladder, broad ligament, uterus.
Patients with ADPKD often present with abdominal pain. Can you name some causes?
Infected cysts
Haemorrhage into a cyst.
The following conditions occur with higher frequency than the general population in patients with ADPKD and also cause abdominal pain.
- diverticulitis/diverticular perforation
- nephrolithaisis
- strangulated/incarcerated hernia
- Ruptured AAA
- Tuberous Sclerosus complex - The gene for ADPKD type 2 is very close to the gene for TSC here certain mutations can cause both
What are the most frequent presenting complaints of PBC?
PBC is asymptomatic in many patients and is diagnosed incidentally e.g. a cholecystectomy.
In those who present with symptoms, pruritis and fatigue are the commonest presenting features.
Some patients experience RUQ Pain.
Impaired bile production leads to impaired absorption of fat soluble vitamins and easy brushing in some patients.
What is the natural history of PBC?
The female:male ratio in PBC is approximately 9:1. AMAs are directed against the mitochondrial enzyme complex M2. The antigen itself is the pyruvate dehydrogenase complex E2 found on the inner mitochondrial membrane. AMA is positive in 90% of patients wit PBC.
In many cases disease progression is so slow that lifespan is unaffected and PBC may diagnosed incidentally e.g. at cholecystectomy. However, symptomatic patients are unlikely to survive more than 2 years
Can you name some conditions that might mimic PBC?
The most common differential diagnoses for PBC are autoimmune hepatitis and primary sclerosing cholangitis.
PBC can occasionally be mistaken for Wilson’s disease as Kayser-Fleischer rings may occur as a result of impaired copper excretion.
Granulomas in the liver may suggest cholestatic sarcoidosis but AMAs are usually absent in this condition
