Gen Med Revision PDF 5

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Gen med revision pdf
Medicine (Queen's University Belfast)
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General Medicine
Michael Grant
Notes based on QUB online Med Portal lectures, QUB student manual, Oxford Clinical
handbook and various external online resources

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General Medicine: Page 2 of 106

Respiratory
Basic anatomy
• The respiratory tract is lined by pseudostratified ciliated columnar cells along with goblet cells; until they
reach the bronchioles which have no cartilage or goblet cells
• All components distal to the terminal bronchioles engage in gas exchange
• Each respiratory acinus (i.e. the collection of respiratory bronchioles and alveoli supplied by a
single terminal bronchioles) has around 2000 alveoli
• The pleural lining is made up of a collagen and & elastin stroma, covered by mesothelium
Pneumonia can be classified by

• Aetiology:
o Viral/bacterial/fungal
• Anatomy:
o Broncho- or lobar
pneumonia
• Clinical:
o Nosocomial or community
Bronchopneumonia is a focal
inflammation of the conductive airways
that spreads to the acini
• More prominent in the lower lobes
• Risk in any immunosuppression (e.g.
diabetes, alcoholism, setroids, malnutrition, HIV/AIDS, COPD, etc.)
• There is a risk post-surgery due to:
o Limited, shallow breathing
o Immune weakening from stress response
o Anaesthetic gases impair mucocillary clearance
• This type comes with a risk of pleurisy and abscess formation
• Can be bilateral
• Histology shows acute inflammation spreading outward form the bronchioles
• Healing is slow and Rx consists of: O2 therapy, ABx and Physio
Lobar pneumonia is when an entire lobe is uniformly inflamed

• Can extend to pleura and cause pleural effusion
o If bacteria spread to effusion, can lead to empyema (i.e. infective pus in the
pleural cavity)
• Typical presents with:
o Fever
o Productive cough (e.g. Rusty sputum is indicative of S. Pneumoniae)
o Pleuritic pain
• Typical pathogens in community are:
o S. Pneumonia - test for urinary antige, can appear with herpes labialis
o H. Influenzae – common in COPD but otherwise no clinical features
differentiate it
o S. Aureus - Usually only a secondary bacterial infection after a viral one or
staph septicaemia
§ Pneumothorax, effusion and empyemas are common and secondary septicaemia may occur with distal abscess
formation
§ Bilateral cavitating bronchopneumonia.
§ Even with IV Flucloxacillin, there is 25% mortality
• Atypical mostly cause an interstitial pneumonia (i.e. inflammation of the parenchyma surrounding alveoli) and dry cough. Causes include:
o Mycoplasma can cause vague flu-like symptoms (headache, myalgia, arthralgia)with normal CXR
§ Look out for myocarditis, erythema multiforme, haemolytic anaemia, Guillain–Barré syndrome & meningoencephalitis
§ On CXR: reticular-nodular shadowing or patchy consolidation often of 1 lower lobe
§ Treat with macrolide
o Legionella pneumophila typically involves some contact with stagnant water
§ Suspect if 3 of 4 of: prodromal viral illness, confusion, lymphopenia, hyponatraemia
§ Anitgen detection in blood or urine with CXR showing bi-basal consolidation.
§ Clarithromycin or Rifampicin
o Chlamydiophila psittaci should be suspected especially if there is a history of bird contact (esp. parrots)
§ Additional symptoms include muscular pains that my last many months
§ Can mimic meningism
§ Look for serum antibody
§ Rx: Marcolides
Michael Grant
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o Chlamydophila pneumoniae is the commonest chlamydial infection. Person-to- person spread occurs causing a biphasic illness:
pharyngitis, hoarseness, otitis, followed by pneumonia. Diagnosis: Chlamydophila complement
fixation test
• Hospital acquired are typically gram negative (60%) such as K. Pneumonia (Red current sputum with a
cavitating pneumonia of the upper lobes), E. Coli, Pseudomonas, Proteus, Enterobacter
• Anaerobes are seen in Mendelson’s syndrome when gastric contents are aspirated causing destructive
changes from acids and colonisation from GI bacteria – therefore best treated with metronidazole
• Also be aware of AIDS-associated Pneumocystis Jiroveci, which produces a pink, frothy exudate in the
alveoli
o Rx: high-dose co-trimoxazole (p410–p411)
• Important to follow-up at risk groups with CXR 6 weeks post-Rx, to eliminate risk of neoplasm
Stages of pneumonia:
1. Congestion/Consolidation/Oedema (24 hours)
a. Heavy red lobe with cough and pleurisy
b. Inflammatory exudate, with initially few neutrophils, disrupts gas exchange
2. Red hepatisation (2-3 days)
a. Solid, Liver-like consistency
b. Packed with neutrolphils, RBCs and fibrin in exudate
3. Grey hepatisation (5-8 days)
a. Firm and dry lung
b. Colour lost, starting from the hilum, as the RBCs lyse and the pressure in alveolar spaces
compresses capillaries leaving a fibrinosuppurative exudate
4. Resolution
a. Reabsorption of lung structure as exudates within the alveoli are enzymatically digested and
resulting debris ingested by macrophages
b. Severe infections can cause healing by organisation that can lead to scarring and pleural
adhesions
Complications of pneumonia include:

• Respiratory failure
• Hypotension - may be due to a combination of dehydration and vasodilatation due to sepsis
• Atrial fibrillation is quite common, particularly in the elderly. It usually resolves with
treatment of the pneumonia Beta-blocker or digoxin may be required
• Pleural effusion - If bacteria spread to effusion, can lead to empyema
• Lung abscess
Lung abscess is a suppuration (collection of pus) that has been walled off by granulation and fibrous
tissue – differing from empyema which makes use of an existing anatomical cavity.
• They form across parenchyma and thus – unlike bronchiectasis – can be fed by more than one
airway
• Primary abscesses are not preceded by other inflammatory processes and are typically due to
aspiration or pulmonary infarction
• Secondary abscesses occur in relation to an underlying condition, such as:
o Pneumonia (esp. Staph Aureus and Klebsiella)
o Obstruction by foreign body or bronchial carcinoma
o Spread from Subphrenic or hepatic abscess
o Septic emboli (e.g. from endocarditis, IV drug use)
o Bronchiectasis
• Complications:
o Rupture and expiration – typically followed by quick recovery
o Rupture and spread – leading to a pneumonia
o Long term presence can cause a cause of fibrous tissue to epithelium, thus becoming a cyst
o Pneumatocele or Cavitating lesion formation – in which air enters the abscess cavity but
cannot escape, leading to an air-filled space within the parenchyma
§ CXR: can be seen to contain air-fluid levels
§ If it ruptures, can release air into the
pleural space causing a
hydropneumothorax (image to the right)
which is seen on erect CXR with a straight
fluid level (no meniscus as seen in
effusion) with the superior pleura
detached from chest way due to air
Michael Grant
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Bronchiectasis is a disease defined by localised, irreversible dilation of part of the
bronchial tree due to the destruction of muscle and elastic tissue – leading the vessels to
be prone to collapse. This is due to Chronic infection of the bronchi and bronchioles
leading to permanent dilatation of these airways.
• Main organisms: H. influenzae; Strep. pneumoniae; Staph. aureus; Pseudomonas
aeruginosa.
• It is an obstructive disease
• Clinical features
o Symptoms: persistent cough; copious purulent sputum; intermittent
haemoptysis
o Signs: finger clubbing; coarse inspiratory crepitations; wheeze (asthma,
COPD, ABPA)
o Complications: pneumonia, pleural effusion; pneumothorax;
haemoptysis; cerebral abscess; amyloidosis.
• Causes include:
o Obstruction by tumour or foreign body
o Childhood pneumonia
o Cystic fibrosis
o Post-infective: Measles; pertussis; bronchiolitis; pneumonia; TB; HIV
o Allergic bronchopulmonary aspergillosis
o Hypogammaglobulinaemia
o Rheumatoid arthritis
o Ulcerative colitis;
o Immotile cilia syndrome (a.k.a. Kartagener’s syndrome)
o Young's syndrome (causing vicious, lipid rich bodily fluids)
o Idiopathic
• Management:
o Postural drainage should be performed twice daily
o Chest physiotherapy may aid sputum expectoration and mucous drainage.
o Antibiotics should be prescribed according to bacterial sensitivities
o Bronchodilators (e.g. nebulized salbutamol) may be useful in patients with
asthma, COPD, CF, ABPA
o Corticosteroids (eg prednisolone) for ABPA
o Surgery may be indicated in localized disease or to control severe haemoptysis.
• Complications:
o Lung abscess
o Empyema (although this is relatively rare as the pleural space in bronchiectasis is
often obliterated)
o Cor pulmonale (Rare but more common if CF is cause)
o Septic emboli (can cause brain abscess) Increased interstitial shadows/fibrotic changes,
o Secondary amyloidosis (can lead to hepto/renal failure) pleural thickening
o Immune complex vasculitis
Chronic obstructive pulmonary disease (COPD) is a common progressive disorder characterized by airway obstruction (FEV1 <80%
predicted; FEV1/FVC <0.7) with little or no reversibility.is a chronic/recurrent obstruction of airflow from a combination of bronchitis and
emphysema, which are pathologies of the airways and alveoli respectively, the most important factor in which is smoking. This obstruction can
lead to ulceration and squamous metaplasia.
• Two classifications; Pink puffers and blue bloaters (ends of a spectrum):
o Pink puffers have increased alveolar ventilation, a near normal PaO2 and a normal or low PaCO2. They are breathless but are
not cyanosed. They may progress to type 1 respiratory failure
o Blue bloaters have decreased alveolar ventilation, with a low PaO2 and a high PaCO2. They are cyanosed but not breathless
and may go on to develop cor pulmonale. Their respiratory centres are relatively insensitive to CO2 and they rely on hypoxic
drive to maintain respiratory effort.
• Clinical features:
o Symptoms: Cough; sputum; dyspnoea; wheeze
o Signs: Tachypnoea; use of accessory muscles of respiration; hyperinflation; reduced cricosternal distance (<3cm); reduced
expansion; resonant or hyperresonant percussion note; quiet breath sounds (eg over bullae); wheeze; cyanosis; cor pulmonale
• Complications: Acute exacerbations ± infection; polycythaemia; respiratory failure; cor pulmonale (right heart failure caused by chronic
pulmonary arterial hypertension seen with oedema & increased JVP); pneumothorax (ruptured bullae); lung carcinoma
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Chronic bronchitis is defined as the production of sputum for 3 months in 2 consecutive
years; seen as:
• Mucus hypersecretion and a change from seromucinous to mucinous appearance
• Mucus gland hyperplasia in which the component of the bronchial wall made up of the
glandular layer increase – this is measured by the Reid Index (thickness of gland
layer/thickness of bronchial wall) with a normal value of 0.3 (than can double in chronic
bronchitis)
o Surface epithelium can see an increase of goblet cells due to metaplasia of other
cells due to inflammation
• Bronchiole obstruction from oedema
Emphysema is a permanent dilation of airspaces distal to the terminal bronchiole that occurs
without fibrosis. Its 3 forms are named based on the location of pathology:
• Paraseptal occurs at the edges of the lung lobules and pleura – caused by inherited or
autoimmune (unknown exact cause)
o Can be a cause in spontaneous pneumothorax
• Panacinar involving entire acinus causing “cotton candy lung” – usually in all or the lower
lobes.
o This is seen in alpha1-antitripsin deficiency.
• Centriacinar involving respiratory bronchioles destroying alveolar septa
o Seen in the upper lobes of smokers, which see “smoke rise” and form bullae (airspace
>1cm)
Asthma is seen as reversible obstruction due to bronchospasm from hyper responsive bronchi. Seen
clinically as a wheeze, SOB and cough. It is usually linked to a type 1 hypersensitivity.
• Divided into:
o Extrinsic – most commonly involves a Type 1
hypersensitivity IgE component, starting in childhood
and seen with PMHx or FHx of atopy
o Intrinsic – associated with bronchial asthma (a.k.a.
bronchitis) with aspirin, exercise, cold temperatures or
infection
• Usually worse in the mornings with a marked diurnal variation in
peak flow (>20%) over the course of 3 days in a two week period
of measure
o On spirometry, 15% improvement after appropriate
beta agonist therapy
o For children, diagnosis sometimes made on clinical features after the age of 2
• Cross-linking of IgE on the surface of mast cell, in response to an allergen, releases inflammatory cytokins leading to bronchoconstriction,
increased mucus secretion and oedema
• Histologically, this is seen as:
o Charcot-Leyden crystals in the mucus - formed from the breakdown of eosinophils
o Mucus plugs
o Creola bodies – clumps of epithelium sloughed into the sputum
o Curschmann’s spirals – formed of condensed mucus
o Hypertrophy of bronchial tissue
o Thickening of basement membrane
• Degrees of asthma attack:
o Mild – dyspnoea, wheeze and cough (+/- sputum)
o Moderate – as above plus hyperinflation (hyper
resonant, polyphonic wheeze)
o Severe - <50% expected PEFR, inability to complete
sentence, increased HR & RR, decreased BP
§ Serial ABGs every 15 minutes
o Life threatening - <33% PEFR, silent chest, cyanosis,
decreased HR & RR, exhaustion, confused/reduced GCS
§ CXR indicated
• Emergency management: give 10 puffs and if no improvement

ring ambulance, the in hospital:
o Oxygen
o Help – airway team and ring ICU for bed
o Salbutamol – 5mg-oxygen driven nebs, back-to-back
o Hydrocortisone – 100mg IV
o Ipratropium bromide – 0.5mg neb every 4-6 hours
o Theophylline – Aminophylline (5mg/kg loading if not on
theophylline) at 0.5mg/kg
o Magnesium – 2g IV
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o Escalate to ICU doctor
• Admission criteria for asthma:
o Any life threatening – remain
in hospital until stable for 24hr
on the TTO medications
o Any degrees that do not get
>75% PEFR by 1 hour after
initial Rx
• Discharge care:
o Specialist nurse for PEFR
technique and monitoring
advice
o Educational psychologist if
young and missing school
o GP for review of Rx in 1 week
o Specialist doctor for
outpatient clinic in 4 weeks
Tuberculosis is a chronic recurrent

infection caused by mycobacterium
tuberculosis – it can occur almost
anywhere in the body (GI tract, CNS,
Lymph nodes, etc.) but classically affects
the lungs; especially in the elderly,
immunosuppressed or malnourished.
• The organism can be seen with a ziehl-neelsen stain but can take weeks to culture – thus PCR is useful
• Caseating granulomatous inflammation is the hallmark of TB and is seen with
Langhan’s giant cells (formed by the fusion of epithelioid histocytes cells –
activated, stationary macrophages resembling epithelial cells - and contain nuclei
arranged in a horseshoe-shape) in a granuloma, a structure walled off by
fibroblasts with layers of lymphocytes and activated macrophages surrounding a
central area of necrosis.
• Infections can present non-specifically with constitutional symptoms (weight loss,
fevers, fevers of unknown origin, hyperhidrosis, generalized hyperhidrosis, chronic
pain, fatigue, dyspnoea, and malaise) plus or minus classic pneumonia signs.
• Primary TB starts with an initial lesion known as a ghon focus; typically, not in the
upper lobe. If there is hilar lymph node involvement, it is known as a ghon
complex. After primary immune response, some pathogen remains dormant in
scars.
• Secondary/reactivation TB can occur and produce cavity lesions in the upper lobes. This can
cause complications such as:
o TB pneumonia
o Bronchopleural fistula -> empyema
o Amyloidosis
o Miliary TB:
§ Named after the millet seed appearance on CXR, this causes widespread
infection via the bloodsteam and swallowed sputum (most commonly seen
as ulceration at terminal ileum)
o Superimposed infection (e.g. aspergillus)
• Treatment involves a combination of (or all of in the case of MDR TB):
o Rifampicin
o Isoniazid
o Pyramidase
o Ethambutol
Cystic fibrosis is one of the commonest life-threatening

autosomal recessive conditions (1 :2000 live births)
affecting Caucasians. Caused by mutations in the CF
transmembrane conductance regulator (CFTR) gene on
chromosome 7 (>800 mutations have now been identified).
This is a Cl- channel, and the defect leads to a combination
of defective chloride secretion and increased sodium
absorption across airway epithelium. The changes in the
composition of airway surface liquid predispose the lung to
chronic pulmonary infections and bronchiectasis.
Clinical features
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• Neonate: Failure to thrive; meconium ileus; rectal prolapse.
• Children and young adults: Respiratory: cough; wheeze; recurrent
infections; bronchiectasis; pneumothorax; haemoptysis; respiratory
failure; cor pulmonale. Gastrointestinal: pancreatic insuffciency
(diabetes mellitus, steatorrhoea); distal intestinal obstruction
syndrome (meconium ileus equivalent); gallstones; cirrhosis.
• Other: male infertility; osteoporosis; arthritis; vasculitis; nasal polyps;
sinusitis; and hypertrophic pulmonary osteoarthropathy (HPOA).
Signs: cyanosis; finger clubbing; bilateral coarse crackles.
Diagnosis
• Sweat test: sweat sodium and chloride >60mmol/L; chloride usual-
ly > sodium
• Genetics: screening for known common CF mutations should be
considered.
• Faecal elastase is a simple and useful screening test for exocrine
pancreatic dysfunction.
Tests
• Blood: FBC, U&E, LFT; clotting; vitamin A, D, E levels; annual
glucose tolerance test
• Bacteriology: cough swab, sputum culture
• Radiology: CXR; hyperinflation; bronchiectasis.
• Abdominal ultrasound: fatty liver; cirrhosis; chronic pancreatitis;
• Spirometry: obstructive defect. Aspergillus serology/skin test (20% develop ABPA, p168).
• Biochemistry: faecal fat analysis
Restrictive lung disease are those conditions that decrease FVC and are usually caused by processes that lead to lung stiffness; i.e. fibrosis,
cellular infiltration, interstitial oedema.
Lung fibrosis can be:

• Intra-alveolar fibrosis – in which scarring fills the alveolar space (the connective tissue here is
called a masson body)
o Also known as organising pneumonia which is caused by:
§ Unresolved bacterial pneumonia
§ Radiation
§ Severe left sided heart failure
§ Crytogenic organising pneumonia (or Bronchiolitis obliterans organizing
pneumonia (BOOP)) which
• Often seen with existing chronic inflammatory disease such as
rheumatoid arthritis, dermatomyositis, or it can be a side effect of certain medications such as amiodarone
• Responds well to steroids
• Interstitial fibrosis – which collagen deposition between the walls of neighbouring alveoli
and can come from:
o Organisation of Transudate/Exudate typically effecting lower lobes:
§ ARDS
§ Rheumatoid and SLE (Exudate)
§ Idiopathic interstitial pneumonia
§ Chronic oedema (Transudate)
§ Asbestosis (Exudate)
o Granulomatous typically affecting the upperlobes:
§ Sarcoidosis
§ Allergic alveolitis
§ Silicosis (a subtype of pneumoconiosis due to silica inhalation e.g. metal
mining, stone quarrying, sandblasting, and pottery/ceramic manufacture)
§ Chronic Berylliosis (Beryllium poisoning)
• End-state “honey comb” fibrosis – loss of alveolar walls and bronchiolectasis (small airway dilation) that forms
cystic spaces
Pneumoconiosis – literally translating as “dusty lung” due to the nodular appearance – refers to a group of
pathologies caused by inhaled inorganic dust, which is toxic to macrophages causing them to die and release
enzymes that lead to fibrosis, the degree of which depending on the type of dust (e.g. silica = +++fibrosis, carbon
+fibrosis)
• Diseases are named after the inorganic causative agent e.g. silicosis, asbestosis, pneumoconiosis (carbon coal
dust)
• Caplan's syndrome is a combination of rheumatoid arthritis (RA) and pneumoconiosis that manifests as
intrapulmonary nodules, which appear homogenous and well-defined on chest X-ray (image to right)
Asbestosis is caused by inhalation of naturally occurring fibro-silicates - or asbestos - fibres that was commonly used in the building trade for
fire proofing, pipe lagging, electrical wire insulation, and roofing felt. Chrysotile (white, curly asbestos) is the least fibrogenic — crocidolite (blue,
straight – or crocodile-like – asbestos) is the most fibrogenic.
Michael Grant
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• Asbestos bodies are the hallmark of exposure caused by macrophages engulfing the asbestos fibres and coating them with iron proteins –
giving them a segments gold/brown appearance
• Exposure can be direct, indirect (families), paraoccupational (healthcare workers), geographic (downwind of factories)
• Clinical features: Similar to other fibrotic lung diseases with progressive dyspnoea,
clubbing, and fine end-inspiratory crackles. Also causes pleural plaques, increased risk of
bronchial adenocarcinoma and mesothelioma.
• Management: Symptomatic. Patients are often eligible for compensation through the UK
Industrial Injuries Act.
• Complications:
o Pleural plaques are circumscribed, fibrotic and often calcified lesions on the parietal &
diaphragmatic pleura
o Pleural effusion/Fibrosis > can lead to atelectasis
o Asbestosis is bilateral fibrosis in the lower lobes, due to high exposures
o Malignant mesothelioma is a tumour of mesothelial cells that usually occurs in the
pleura, and rarely in the peritoneum or other organs. It is associated with occupational
exposure to asbestos but the relationship is complex.60 90% report previous exposure
to asbestos, but only 20% of patients have pulmonary asbestosis. The latent period between exposure and development of the
tumour may be up to 45yrs. Compensation is often available.
§ Clinical features: Chest pain, dyspnoea, weight loss, finger clubbing, recurrent pleural effusions. Signs of metastases:
lymphadenopathy, hepatomegaly, bone pain/tenderness, abdominal pain/obstruction (peritoneal malignant mesothelioma).
§ Tests: CXR/CT: pleural thickening/effusion. Bloody pleural fluid
§ Diagnosis is made on histology, usually following a thoracoscopy
§ Management: Pemetrexed + cisplatin chemotherapy can improve survival.61 Surgery is hard to evaluate (few randomized trials).
Radiotherapy is controversial. Pleurodesis and indwelling intra-pleural drain may help.
Acute Respiratory Syndrome (ARDS) is seen as diffuse alveolar damage, arising from a non-
specific alveolar injury or secondary to a systemic illness. Lung damage and release of
inflammatory mediators cause increased capillary permeability and non-cardiogenic
pulmonary oedema, often accompanied by multi-organ failure.
Causes
• Pulmonary: Severe pneumonia; gastric aspiration; toxic inhalation (including
drowning); injury; vasculitis; contusion
• Other: Shock; septicaemia; haemorrhage; multiple transfusions; DIC; pancreatitis; acute
liver failure; trauma; head injury; malaria; fat embolism; burns; obstetric events
(eclampsia; amniotic fluid embolus); drugs/toxins (aspirin, chemotherapy, heroin,
paraquat).
Clinical features
Cyanosis; tachypnoea; tachycardia; peripheral vasodilatation; bilateral fine inspiratory
crackles.
Investigations
FBC, U&E, LFT, amylase, clotting, CRP, blood cultures, ABG. CXR shows bilateral
pulmonary infiltrates. Pulmonary artery catheter to measure pulmonary capillary
wedge pressure (PCWP).
Diagnostic criteria
One consensus requires these 4 to exist:
1. Acute onset
2. CXR: bilateral infiltrates
3. Pulmonary capillary wedge pressure (PCWP) <19mmHg or a lack of clinical
congestive heart failure.
4. Refractory hypoxaemia with reduced PaO2 despite increase RR: FiO2 <200 for
ARDS
Management: Admit to ITU; give supportive therapy; treat the underlying cause.
• Respiratory support in early ARDS, continuous positive airway pressure
(CPAP) with 40–60% oxygen may be adequate to maintain oxygenation. But
most patients need mechanical ventilation.
• Circulatory support Invasive haemodynamic monitoring with an arterial line
and Swan–Ganz catheter (pulmonary artery catheterization) aids the
diagnosis and may be helpful in monitoring PCWP and cardiac output.
Maintain cardiac output and O2 delivery with inotropes (e.g. dobutamine
2.5–10μg/ kg/min IVI), vasodilators, and blood transfusion.
• Sepsis Identify organism(s) and treat accordingly. If clinically septic, avoid nephrotoxic antibiotics.
• Other: Nutritional support: enteral is best. Steroids protect those at risk of fat embolization and with pneumocystosis (Jiirovecii) and may
improve outcome in subacute ARDS
Complications
Diffuse alveolar damage can be divided into stages:
• Exudative can last around 1-week blood and fluid in the airspaces with a hyaline membrane (formed of a layer of fibrin and necrotic
pneumocytes)
Michael Grant
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• Regeneration with an increasing number of type 2 pneumocytes
• Repair either by resolution (exudate broken down and reabsorbed) or by
organisation (causing interstitial fibrosis)
Extrinsic allergic alveolitis is effectively asthma of the alveolus due to an exposure

to an extrinsic protein. In sensitized individuals, inhalation of allergens (fungal
spores or avian proteins) provokes a hypersensitivity reaction. In the acute phase,
the alveoli are infiltrated with acute inflammatory cells. With chronic exposure,
granuloma formation and obliterative bronchiolitis occur.
Pathology
• Acute exposure is a type 2 hypersensitivity reaction
• Repeated exposure is a type 4 and can lead to complications
Causes
• Bird-fancier’s and pigeon-fancier’s lung (proteins in bird droppings)
• Farmer’s and mushroom worker’s lung (Micropolyspora faeni,
Thermoactinomyces vulgaris).
• Malt worker’s lung (Aspergillus clavatus).
• Bagassosis or sugar worker’s lung (Thermoactinomyces sacchari).
Clinical features
• 4–6h post-exposure: Fever, rigors, myalgia, dry cough, dyspnoea, crackles (no wheeze)
• Chronic: Increasing dyspnoea, weight loss, exertional dyspnoea, type I respiratory failure, cor pulmonale
Complications
• Granulomas
• Interstitial fibrosis
• Respiratory failure
Tests
Acute:
• Blood: FBC (neutrophilia); ESR up;
• ABGS; positive serum precipitins (indicate exposure only).
• CXR: upper-zone mottling/consolidation; hilar lymphadenopathy (rare)
• Lung function tests: reversible restrictive defect; reduced gas transfer during acute attacks
Chronic:
• Blood tests: positive serum precipitins
• CXR: upper-zone fibrosis; honeycomb lung.
• Lung function tests: persistent changes (see above).
• Bronchoalveolar lavage (BAL) fluid shows lymphocytes and mast cells.
Management
Acute: Remove allergen and give O2 (35–60%), then: Oral prednisolone (40mg/24h PO), followed
by reducing dose.
Chronic: Avoid exposure to allergens, or wear a facemask or +ve pressure helmet. Long-term
steroids often achieve CXR and physiological improvement. Compensation (UK Industrial Injuries
Act) may be payable.
Sarcoidosis is a multisystem granulomatous disease that usually affects the lungs and their hila.
• Common in northern Europe
• Decreased risk in smokers
• Fatal in 5-10%
Clinical features
• Often presents with erythema nodosum ± polyarthralgia
• Constitutional
• Based on location of granuloma; can cause almost any symptom
• Hypercalcaemia
• Raised ACE
Pathology
• Langhan’s giant cell
• Asteroid bodies
• 25% develop pulmonary
• Asteroid bodies
• Non-caseating granulomas
• 25% develop pulmonary
Michael Grant
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Pulmonary oedema is caused by a shift of water into the lungs and like all oedema it is effected by:
Hydrostatic pressure, oncotic pressure and vascular permeability.
Causes can be divided into their mechanism:
• Increased hydrostatic pressure
o Left sided failure
o Supra- or ventricular tachycardia
o Mitral valve disease
o Left atrial myxoma
o Pericarditis
o Fluid overload (also dilutes plasma protein reducing oncotic pressure also)
o Veno-occlusive disease of the lung
• Increased capillary permeability
o ARDS (Cytotoxic oedema)
o Cerebral injury (from increased sympathetic activity)
o Renal failure (increased fluid with hyperuraeima)
o High altitude (hypoxia -> vasoconstriction)
Clinical features
• SOB
• Orthopnoea
• Cough (pink frothy sputum)
• Paroxysmal nocturnal dyspnoea
• On CXR: Kerley B lines (short horizontal lines near the lung Bases,
that represent interlobular sceptum fluid) and batwing oedema (image to right)
Microscopic features
• Pink fluid in alveoli
• Congested capillaries (beads on a string)
• Heart failure cell (macrophages filled with yellow-brown granules of haemosiderin)
Pleural effusion is an excess of fluid that accumulates in the pleural cavity. Unless there is gross cardiac failure
present, a diagnostic tap should be performed – looking for MC&S, cytology, pH (unless purulent, LDH and
protein to determine if cause is:
• Serous fluids
o Transudates contain reduced protein and are typically caused by failures (raised hydrostatic or
reduced oncotic pressure); CCF, Cirrhosis, Nephrotic syndrome, peritoneal dialysis and
hypothyroidism
o Exudates contain and increased amount of protein and are due to irritation of the lung (increased
capillary permeability); infection, malignancy (must be ruled out in >60yo), autoimmune (SLE, RA,
Goodpastures), Boerhaave syndrome (oesophageal rupture due to excessive vomiting)
• Pus
o Empyema usually secondary to a bad pneumonia
Pulmonary neoplasms are the most common form of primary malignant tumour
Risk factors: Cigarette smoking is the major risk factor

Others: asbestos, chromium, arsenic, iron oxides, and radiation (radon gas).
Histology:
• Squamous (35%) typically central in the main bronchus seen with keratin pearls
• Adenocarcinoma (27%) typically peripheral and produces mucin
o Most common in non-smokers
o Associated with pulmonary fibrosis
• Small cell (20%) typically in the hilar region are seen with densely packed small,
round cells of a blue colour (due to little cytoplasm)
o High risk of paraneoplastic syndromes
o Poor prognosis (3-6 months)
o Treatment only by chemo or radiotherapy
• Other: large cell (10%); alveolar cell carcinoma (rare, <1%).
o Bronchial Carcinoids (unlike appendix carcinoids) are invasive but less so than carcinomas
Michael Grant
lOMoARcPSD|4927727

§ Account for 5% of lung tumours and usually form a central, polypoid projection made of neuroendocrine cells forming nests that
can secrete vasoactive serotonin (this can cause carcinoid syndrome flushing and diarrhea, and, less frequently, heart failure
and bronchoconstriction)
§ Surgery curative in 90-95% of cases
Clinically the most important division is between small cell (SCLC) and non-small cell (NSCLC).
Symptoms: Cough (80%); haemoptysis (70%); dyspnoea (60%); chest pain (40%); recurrent or slowly resolving pneumonia (be suspicious,
especially in elderly); lethargy, anorexia; weight loss.
Signs: Cachexia; anaemia; clubbing; HPOA (hypertrophic pulmonary osteoarthropathy, causing wrist pain); supraclavicular or axillary nodes.
Chest signs: none, or: consolidation; collapse; pleural effusion.
Metastases: bone tenderness; hepatomegaly; confusion; fits; focal CNS signs; cerebellar syndrome;
proximal myopathy; peripheral neuropathy.
Complications:
• Local: recurrent laryngeal nerve palsy (causing hoarseness); phrenic nerve palsy (causing a
raised hemidiaphram); SVC obstruction (especially by small cell); Horner’s syndrome
(Pancoast’s tumour); Pancoast syndrome (Shoulder pain radiating to axilla, atrophy of
hand/arm muscles, Horner syndrome, Oedema from vessel compression); rib erosion;
obstructive pneumonia; pericarditis; AF.
Metastatic: brain (particularly cerebellum); bone (bone pain, anaemia, raised Ca2+); liver; adrenals (Esp.
small cell, can trigger Addison’s).
Endocrine/Paraneoplastic syndrome: ectopic hormone secretion, eg SIADH and ACTH (Cushing’s) by small cell
tumours; PTH (`Ca2+) by squamous cell tumours.
Non-metastatic neurological: confusion; fits; cerebellar syndrome; proximal myopathy; neuropathy; polymyositis; Eaton-Lambert syndrome
(antibodies are formed against presynaptic voltage-gated calcium channels)
Secondary lung neoplasms can arise from different systems especially:

• Renal cell carcinoma produces cannonball lesions
• Lymphangitis carcinomatosa is inflammation of the lymph vessels caused by a malignancy and, in the lung, is usually due to a breast
cancer metastasis that typically blocks lymphatic drainage by a mass near the hilum.
Pleural tumours are more commonly secondaries, however one notable primary is:
• Malignant mesothelioma spreads diffusely over the entire lung surface, eventually crushing it and causing dead by respiratory failure
o Due to asbestos in 90% of cases and can be latent for many years (25-40), however other causes are:
§ Non-asbestos fibre (e.g. volcanic silcates, erionite)
§ Simian virus 40
o Classified as epithelial (60%), sarcomatous (15% and has worst prognosis), Mixed (25%)
o Typically seen with recurrent pleural effusions, chest pain and dyspnoea
Michael Grant
lOMoARcPSD|4927727

Cardiology
ECG interpretation
Perform and interpret an Electrocardiograph
o Consent, remove upper body clothing and lie down
o Remove excess hair where necessary
o Stickers over bone
o Ask the patient to relax and lie still
3 Lead ECG:
3-lead system approximates to I, II, III
Apply sensors:
o Colour coded (Red: right arm, Lemon: left arm, Green: left leg)
12 Lead ECG:
More sophisticated, 3D interpretation of the electrical activity of the heart
10 electrodes (Red, Lemon, Green, Black, V1-V6) produce the 12 leads:
• Bipolar Leads (I, II, III)
o Reference point on one limb, ‘sensing’ electrode on another
o Lead I ‘looks’ left. (LA-RA)
o Lead II towards left foot from the right (LL- RA)
o Lead III towards left foot from the left (LL- LA)
• Augmented limb leads (aVR, aVL, aVF)
o Use same electrodes positions as I,II,III
o Formula used to allow different views of the heart to be combining vectors
from those leads (Wilson’s central terminal)
o aVF points directly down.
o
o aVL points 30 north of lead I
o aVR ‘looks’ at the heart from up and right, deflections are therefore negative
• Chest leads (V1-V6)
o Looks at the heart cross-sectional axis
th
o Septal leads: V1, V2 (either side of sternum in 4 ICS)
o Anterior leads: V3 (inbetween V2 & V4), V4 (5th ICS MCL)
o Lateral leads: V5 (inbetween V4 & V6), V6 (5th ICS mid axillary line)
o R waves progress from being less dominant, mixed and onto dominant as you go
from lead V1 to V6
• R Waves should become more positive and less equiphasic from V1 to V6
ECG Waveforms:
• P wave = Atrial depolarization
• PR interval = 0.12-0.20 secs (3-5 small squares) is produced by
a physiologic delay at the AV to allowing for ventricular filling
• QRS complex = ventricular depolarisation (0.08 - 0.12 secs)
o Q wave: representing depolarization of bundle of His,
which it does from left to right in the opposite direction
to the main conduction (right to left) causing a small,
downward deflection (from the perspective of Lead II)
o R wave: Ventricular depolarization toward the
direction of lead II. More muscle, more cells, more electricity leads to a bigger wave.
o S wave: Depolarisation of the Purkinje fibres causes negative deflection (in lead II)
as it represents the last, more superior, compents of the ventricles contracting (given
that ventricles contract from apex upward)
• If the R-wave > S-wave: depolarisation is moving towards that lead
• If the R-wave < S-wave: depolarisation is moving away from that lead
• If the R-wave = S-wave: depolarisation is travelling at exactly 90° to that lead
• QT interval = <0.44sec but will vary with heart rate
o Affected by antiarrhythmics, antibiotics, tricyclic antidepressants, kalaemia
• ST segment: end of the S wave to the start of the T wave and should be flat or slightly
upsloping
o Elevation: if elevated in a few leads (>2mm chest, >1mm limb) indicates the
Small square = 0.04sec, Large square = 0.2sec
possibility of MI
• If in most leads, question possibility of pericarditis, especially if PR depression
• Concave elevation in all 12 leads is diagnostic of pericarditis
o Depression is diagnostic of ischaemia
• However, beware aware of digoxin’s “reverse tick” ST depression
• T wave = Ventricular repolarization
Michael Grant
lOMoARcPSD|4927727

o Inversion implies ischaemia/infarction as usually positive in all leads
o Hyperkalaemia (“Tall tented T waves”)
Cardiac axis:
• The cardiac axis gives us an idea of the overall direction of
electrical activity when the ventricles are contracting
• Normal axis: In healthy individuals you would expect the axis to lie between -30°
and +90º
o Thus overall direction of electrical activity is towards leads I,II & III (green
segment) giving them all positive deflection – thus is is useful to use
these three leads when trying to make decisions about the axis
o And the most negative in aVR (as it looks at the heart from the opposite
direction)
• Right axis deviation (RAD): is usually caused by right ventricular
hypertrophy, causing the overall direction of electrical activity is distorted to
the right (between +90º and +180º)
o Thus deflection in Lead I becomes more negative & the
deflection in Lead III more positive
o Usually when right side has to work harder (RVH, chronic
lung disease, pulmonary hypertension, pulmonary
embolism, ASD, VSD) or when left side works less (Left
posterior fasicular block, lateral MI); although it can be
normal in children and very tall, thin people
• Left axis deviation (LAD): direction of overall electrical activity
becomes distorted to the left (between -30° and -90°)
o This causes the deflection in Lead I and aVL to become
more positive & the deflection in Lead III to be more negative
o Usually when left side has to work harder (LVH, Pregnancy) or when right side works less (RBBB, inferior MI);
o Common causes of LAD include left ventricular hypertrophy (LVH), inferior MI, left anterior fascicular block (or hemiblock) and, rarely,
Wolff-Parkinson White syndrome
Bundle Branch Block:

• Seen as a wide QRS complex despite sinus rhythm (QRS width >0.12sec (>3 small
squares))
• Look at QRS complexes in the V1 & V4/5/6 (LBBB, RBBB “WilliaM MorroW”)
• Left bundle-branch block:
o Complete LBBB block is seen with a QRS of >0.12sec
o The depolarisation wavefront travels in more or less the normal direction in LBBB,
the deflections seen are generally normal.
o However, because of the abnormal sites of initiation (from the right ventricle
rather than the conduction system) the electric heart vector makes a slower and
larger loop to the left and is seen as a broad and tall R-wave, usually in the
lateral leads: leads I, aVL, V5, or V6.
o The following pattern is seen: QRS >0.12s, ‘M’ pattern in V5, no septal Q waves,
inverted T waves in I, aVL, V5–V6.
o Causes include: Cardiomyopathy, Acute MI, Hypertension, Aortic valve disease
• Right bundle-branch block:
o Occurs when the RBB is defective so that the electrical impulse cannot travel
through it to the right ventricle; thus, depolarisation reaches the right
ventricle through the left ventricle, after it depolarises, via the septum.
o This is slower than the conduction system and leads long QRS-complex
(>0.12sec)
o activation of the right ventricle is so much delayed, that it can be seen following
the normal activation of the left ventricle
o RBBB causes an abnormal terminal QRS-vector that is directed to the right
ventricle (i.e., rightward and anterior). This is seen in the ECG as a broad
terminal S-wave in lead I and a double R-wave in lead V1
o The following pattern is seen: QRS >0.12s, ‘RSR’ pattern in V1, dominant R in V1,
inverted T waves in V1–V3 or V4, deep wide S wave in V6
o Causes include: Normal variant, COPD, PE, ASD, VSD, tricuspid/pulmonary
valvular disease (due to proximity to bundle).
Michael Grant
lOMoARcPSD|4927727
SA nodal block:
• SA blocks rarely give severe symptoms, because even if an individual had complete block at this level of the conduction system (which is
uncommon), the secondary pacemaker of the heart would be at the AV node, which would fire at 40 to 60 beats a minute, which is
enough to retain consciousness in the resting state.
• SA block is capable of causing problematic symptoms even so, and may also hint at conduction issues elsewhere in the heart, and
therefore SA blocks are - despite their lower level of life-threatening risk - still "the most common indication for pacemaker implantation in
the US"
• Sinus node dysfunction can result from either:
o Failure of the P cells to produce an impulse. This leads to sinus pauses and sinus arrest.
o Failure of the T cells to transmit the impulse. This leads to sino-atrial exit block.
• Types of SA nodal blocks include:
o First Degree SA block - Delay between impulse generation and transmission to the atrium.
§ No changes on ECG It can be detected only during an electrophysiology study when a small wire is placed against the SA node,
o Second degree SA block Wenckebach (Mobitz I) - progressive lengthening of the interval between impulse generation and
transmission, culminating in failure of transmission
§ Gradually lengthening transmission interval pushes successive P waves closer together resulting in grouping of the P-QRS
complexes.
o Second degree SA block Mobitz II - Intermittent dropped P waves with a constant interval between impulse generation and atrial
depolarisation
§ There is no clustering of P-QRS complexes seen with intermittent P waves “droping out” of the rhythm, while subsequent P waves
arrive “on time”.
o Third degree SA block or “node exit” block - None of the sinus impulses are conducted to the right atrium.
§ There is a complete absence of P waves producing long sinus pauses or sinus arrest (may lead to fatal asystole) but rhythm may
be maintained by a junctional escape rhythm.
• In addition to the above blocks, the SA node can be suppressed by any other arrhythmia that reaches it. This includes retrograde
conduction from the ventricles, ectopic atrial beats, atrial fibrillation, and atrial flutter.
AV Block:
• Can be caused by Lyme disease and SLE

• In Mobitz type 2; it is important to clarify the frequency of lost beats, i.e.
number of P waves for every missed QRS; 2:1, 3:1, 4:1, etc.
rd
• In 3 degree/complete block: The ventricular escape beat follows a long pause in ventricular rhythm and acts to prevent cardiac arrest.
An escape beat is a form of cardiac arrhythmia, in this case known as an ectopic beat. It can be considered a form of ectopic pacemaker
activity that is unveiled by lack of other pacemakers to stimulate the ventricles.
o Ventricular pacemaker cells discharge at a slower rate than the SA (70bpm) or AV node (40-60bpm), usually the rate is thus reduced
by 15-40 beats per minute
o The atrial rate is approximately 100 bpm.
o The ventricular rate is approximately 40 bpm
o Stokes Adams attack: Sudden collapse into unconsciousness due to a disorder of heart rhythm in which there is a slow or absent
pulse resulting in syncope (fainting) with or without convulsions
Michael Grant
lOMoARcPSD|4927727
ECG interpretation:
ECGs are RAWW data
• Rate: Number of large squares between R waves, divided by 300
• Rhythm: Look at the R-R intervals again – if they are equally spaced from each other the rhythm
is regular? Use sticky note to check quickly.
• Axis: Look at leads I, II and III – are they all positively deflected?
• Waveform, ride from start to finish:
o P waves present? All followed by a QRS?
§ P mitrale: bifid P wave, indicates left atrial hypertrophy. P pulmonale:
peaked P wave, indicates right atrial hypertrophy.
o PR interval 0.12-0.20secs? PR depression (Pericarditis or atrial infarction)?
o Pathological Q waves are usually >0.04s wide and >2mm deep. Usually as
sign of previous infarction
o QRS width 0.08-0.12? Large amplitude – LVH? Check V1 & V6 for WilliaM
MarroW?
o ST elevation (Tombstone, saddle-shaped?)? Depression (with T inversion)?
o T wave inversion? Tall, tented?
Cardiovascular ischaemia and infarction

Ischaemia is the result of an impaired blood flow and perfusion of a tissues, depriving it of
nutrients, which is reversible and the effects of which depend on the duration of the event and the demands of the tissue.
Infarction is the death of tissue by necrosis due to extreme ischaemia, which is irreversible and is inflammatory.
The factors affecting this include:
• Type of supply; i.e. single or
double (such as in the liver
and lungs)
• Rate of occlusion; slower
rate can allow for adaption
• Tissue constituents;
high/low metabolic demand
• Blood constituents;
anaemia/hypoxic versus
normal
Morphology of infarcts:
• Red infarcts occur in tissues
with dual supply – the tissue
infarcts but bleeding still
occurs into the area leaving
it red
• Pale infarcts occur in tissue
with no redundant blood supply – typically solid organs – resulting in a pale lesion
Vascular insufficiency causes can be considered as:

• In the lumen: thrombosis, embolism, atheroma
• In the wall: vasospasm, vasculitis, Mönckeberg's arteriosclerosis (stiffening caused by
calcium deposition in tunica media)
• Outside the wall: Tumour, foreign body, organomegaly
Thrombosis can be divided into:

• Arterial thrombosis in which distal tissues become pale, pulseless, persishingly cold,
painful and paralytic – before undergoing eventual infarction
• Venous thrombosis in which distal tissues becomes swollen, red and tender
Thrombi can meet a number of fates:

• Lysis and resolution
• Organisation – scar tissue forms and completely occludes the vessel
• Recanalisation – flow returns but some there is still residual scar and/or thrombus
• Embolism – fragments break off and lodge downstream (e.g. PE)
o Definition: a mass that can move within the vascular system with the risk of
becoming lodged and obstructive to flow
Michael Grant
lOMoARcPSD|4927727

o Majority derived from thrombi (esp. with DVT as source)
o Other types include: atheromatous, amniotic fluid, gat, fat, tumour, infective
o However, the heart is the greatest source of emboli:
§ Atheroma w/ thrombosis
§ Valve vegetation
§ Atrial thrombus
§ Thrombus from recent of old MI
Atheroma is the deposition of lipids in the

tunica intima caused by the presence of lipids
and continued phagocytosis and death of
macrophages which becomes topped with a
fibrous cap after the invasion of smooth muscle
cells and fibroblasts; most frequently occurring
in high pressure vessels and leads to luminal
narrowing. The morphology can be:
• Fatty streaks that are precursor lesions
consisting of linear elevations of intima
produced by lipid laden macrophages
• Fibrolipid plaque that are bigger
plaques of fat with fibrosis and fibroblast
invasion
• Complicated lesions that have caused additional pathology such as;
narrowing, endothelial erosion & thrombosis +/- emboli, aneurysm
Ischaemic heart disease ranges from angina (stable or unstable), myocardial

infarction and up to sudden death.
Angina Pectoris:
• is typically caused by atheroma but can also be caused by any mismatch in
oxygen supply and demand:
o Reduced supply – atherosclerosis, aortic stenosis, emboli, vasospasm
(Prinzmetal angina – avoid aspirin and B-blockers)
o Increased demand – hypertrophy, thyrotoxicosis
o Decreased O2 content – COPD, anaemia
o Although it is important to note that there may be diffuse myocardial
fibrosis in the asymptomatic and, in sudden death, there may be no
macroscopic changes
• Angina classification (Canadian CVS society):
o Class 1: Only on strenuous activity
o Class 2: Moderate activity
o Class 3: Limitation of ordinary activity
o Class 4: At rest i.e. unstable angina
• Investigations
o ECG (especially looking for pathological Q waves, ST depression or LVH)
o Echocardiogram to assess LV function, valve disease, congenital heart disease,
endocarditis, pericardial effusion
o Exercise stress tests with a ECG looking to provoke some of the ischaemic changes
listed above
§ Contraindications: Recent Q wave MI (<5 days ago) or unstable angina, severe
aortic stenosis, Uncontrolled arrhythmia, hypertension, or heart failure, Acute myocarditis or pericarditis, Acute aortic dissection,
acute pulmonary embolism
§ Stress echocardiogram is used for those not suitable for physical stress by use of a pharmacological agent (e.g. dobutamine) to
look for decreased profusion
§ Stress myocardial scan is a nuclear medicine technique that uses thalium plus physical or pharmacological stress to view
cardiac perfusion
o Ambulatory ECG monitoring (eg Holter monitor) to pick up paroxysmal arrhythmias
§ ‘Loop’ recorders record only when activated by the patient—they cleverly save a small amount of ECG data before the event
§ Can be implanted, such as a Reveal device
o Cardiac catheterisation is used to perform angiography, LVH measurement and intracardial pressures via insertion of a catheter into
the heart via the femoral or radial artery or venous system, and manipulating it within the heart and great vessels.
§ If stenosis is detected, then PCI can be performed at the same time
§ Can cause Loss of peripheral pulse: May be due to dissection, thrombosis, or arterial spasm (1% of brachial catheterizations)
Michael Grant
lOMoARcPSD|4927727

• Treatment:
First line:
Advice + Nitrates + Beta-Blockers/CCBs (usually rate limiting –
e.g. verapamil – however Dihydropyridine can be used if low HR –
e.g. Amlodipine)
Second line: Addition or switch to…
• Ivabradine - acts on the If (f is for "funny") ion current, which
is highly expressed in the sinoatrial node, as a mixed Na+–
K+ inward current. Ivabradine reduces cardiac pacemaker
activity, selectively slowing the heart rate for filling
• Long-acting nitrates - oral nitrates have a longer-lasting
effect, e.g. isosorbide dinitrate (ISDN) and isosorbide-5-
mononitrate (ISMN).
• Nicrorandil (Nitrate plus K+ATP channel agonist – reduces
RhoA which increases calcium efflux from sarcolemma)
• Ranolazine - inhibits persistent or late inward sodium
current (INa) in heart muscle in various Na channels, leading to reductions in elevated intracellular calcium levels. This in turn leads to
reduced tension in the heart wall, leading to reduced oxygen requirements for
the muscle
• Trimetazidine - inhibits beta-oxidation of fatty acids by blocking long-chain 3-
ketoacyl-CoA thiolase, which enhances glucose oxidation. In an ischaemic cell,
energy obtained during glucose oxidation requires less oxygen consumption
than in the beta-oxidation process reducing hypoxia
Third line: Angio plus revascularization…
• Percutaneous Coronary Intervention
• CABG (Can be venous graft [e.g. saphenous] or arterial [e.g. LIMA – left
internal mammary artery])
Acute coronary syndrome encompasses:

• STEMI
• NSTEMI
• Unstable angina
• Presentation:
o Chest pain (not relieved by nitrates)
o Dyspnoea
o Nausea/Vomiting/Sweating – usually in severe
o Be aware of those likely to have atypical presentations; diabetics, female,
elderly and previous CABG
o If beginning to decompensate; pulmonary oedema, tachycardia, hypotension
It is important to catch any patients with ACS but is also important to exclude other
pathologies with similar presentations, such as:
• Pericarditis
• Pulmonary embolus
• Pneumothorax 4PAV
• Peptic ulcer
• Aortic dissection
• Valvular disease
Useful tests include:
• Bloods: Troponin T & I and Creatinine Kinase
• Investigations: ECG, Echocardiogram
• Radiology: CXR, Catheterisation (+/- intervention)
Acute MI:
• Usually affects LAD (most common), RCA or LCCA
• Necrosis of the ventricle is followed by inflammation and fibrous repair –
releasing troponins during this process in a manner than is proportional to the
damage caused
o <24hrs: ECG changes with no macroscopic changes (enlarged
mitochondria seen on electron microscope)
o >24hrs: Pale with inflam. border with loss of myocyte striation
o Days/weeks: Dead myocytes removed by macrophages and fibrosis
o Months: Scar matures and becomes an akinetic section and, potentially, a
weak point in the cardiac tissue
Michael Grant
lOMoARcPSD|4927727

• Complications: DARTTH VADERR
o Sudden Death by VF
o Arrhythmia or heart block (damage to conducting
system)
o Rupture (Myomalacia cordis – soft cardiac muscle -
and rupture can occur 3-5 days post-MI causing
ventricular rupture or spetal defect depending on
location)
o Tamponade and/or pericarditis
o Thrombus
o Heart failure
o Valve disease
o Aneurysm (tends to occur with mature scar later
than myomalacia cordis)
o Dressler’s syndrome (Fever, pleuritic pain,
pericardial effusion, anaemia and raised ESR
around 1–3wks post-MI; thought to be due to neo-
autoimmune reaction to autoantigens released during infarction - rare)
o Mitral Regurgitation (due to damage to papillary muscle and/or chordae tendineae)
o Recurrance
Treatment:
• Initial management of all ACS by MONA
o Offer intravenous opioids such as Morphine, particularly if an acute myocardial infarction is suspected.
o Do not routinely administer Oxygen, but monitor oxygen saturation using pulse oximetry and give if <94% (or aim for 88–92% in
COPD until blood gas analysis is available)
o Prompt administration of GTN (sublingual or buccal)
o Offer people a single loading dose of 300 mg Aspirin ASAP unless allergic – then consider clopidogrel
• For STEMI – follow location guidelines, likely some form of revascularization
• For Unstable Angina or NSTEMI - Offer a loading dose of 300mg clopidogrel in addition to aspirin to patients with no contraindications
(for example, an excessive bleeding risk) and aim to undergo PCI within 24 hours of admission; Offer:
o unfractionated heparin if angiography is likely within 24 hours of admission
§ Fondaparinux to patients without a high bleeding risk unless coronary angiography is planned within 24 hours
§ Adding a glycoprotein IIb/IIIa inhibitor (intravenous eptifibatide or tirofiban) if angiography is scheduled within 96
hours of hospital admission, or bivalirudin (direct thrombin inhibitor) as an alternative to the combination of a heparin
plus a GPI if the patient is not on fondaparinux or a GPI and angiography is scheduled within 24 hours of admission.
• Secondary prevention is particularly important; forget the burgers and have a SALAD:
o Statin
o Aspirin (75mg daily)
o Lifestyle advice (Smoking, diet, exercise… best advice in regard sex following MI is once you can walk up a flight of stairs)
o ACE Inhibitor (or ARB if not tolerated)
o Decreased heart rate (Beta blocker, or rate-limiting CCB if contraindicated)
Hypertension can be classified based on it’s aetiology, i.e. “primary”

(a.k.a. essential – without an underlying cause) or “secondary” to
another pathology. It can also be classified according to clinical signs:
• Benign refers to those with a relatively stable hypertension:
o Diagnose hypertension immediately if systolic >180
mmHg or diastolic blood >110 mmHg (with no eye
symptoms) — and start antihypertensive drug treatment
immediately.
o For other people, suspect hypertension if clinic blood
pressure is >140/90 mmHg. Recheck blood pressure on 2–
3 occasions and if persistently above 140/90 mmHg, offer
ambulatory blood pressure monitoring to confirm the
diagnosis of hypertension:
§ Stage 1 hypertension if clinic blood pressure is above
or equal to 140/90 mmHg, and ABPM average is
above or equal to 135/85 mmHg.
• Treat if <80 years with any of: Target organ
damage, established cardiovascular disease,
renal disease, diabetes, and/or a 10 year
cardiovascular risk of 20% or more
Michael Grant
lOMoARcPSD|4927727

§ Stage 2 hypertension and start antihypertensive drug treatment if clinic blood pressure is above or equal to 160/100 mmHg,
and ABPM average is above or equal to 150/95 mmHg, or there is isolated systolic hypertension with a systolic blood pressure of
160 mmHg or higher.
• Malignant refers to blood pressure undergoing an accelerated increase producing acute damage to organs:
o Arrange same-day admission if there are signs of malignant hypertension (blood pressure 180/110 mmHg or higher with signs of
papilloedema and/or retinal haemorrhage)
o Other than retinal changes, can also produce:
§ Encephalopathy (e.g. headaches, seizures)
§ Renal pathology (e.g. proteinuria, haematuria,
failure)
o Histologically is produces necrosis of arterioles
(fibrinoid necrosis) and hyperplastic arteriolitis (onion-
skinning) that leads to narrowing of lumens that, in turn,
leads to malignant aterioscleriosis and nephrosclerosis
o In general, use oral therapy, unless there is
encephalopathy or CCF (if this is the case – senior help
and intra-arterial labetalol). The aim is for a controlled
reduction in blood pressure over days, not hours. Avoid
sudden drops in BP as cerebral autoregulation is poor
(so stroke risk).
• Causes:
o Renal: CKD (e.g. polycystic, diabetic nephropathy), acute
glomerulonephritis, renal artery stenosis
o Endocrine: aldosteronism (Conn’s), Cushing’s,
pheochromocytoma, hypo/hyperthyroidism,
acromegaly, hyperparathyroidism (via increased Ca)
o CSV: Coarctation of aorta, sleep apnea, obesity, vasculitis (esp. Polyarteritis nodosa – th e “rosary bead” aneurysms typically
produced by a vasculitis typically involving renal and visceral vessels but sparing the pulmonary circulation)
o Drugs: NSAIDs (increased pressure from reduced vasodiliation), OCP,
steroids, immunosuppressants (cyclosporine, tacrolimus), cocaine, alcohol
• Complications:
o Accelerated atherosclerosis: TIAs/Strokes, Renal artery stenosis (vicious
circle), AAA
o Small vessel disease occurs due to hyaline arteriolosclerosis (thickening of
the walls of arterioles by the deposits that appear as homogeneous pink
hyaline), which can lead to:
§ Charcot-bouchard aneurysms in the brain – an outpouching filled with
thrombus
§ Retinopathy seen as flame haemorrhages, papilloedema, hard exudates,
cotton wool spots (areas of micro-infarction)
§ Benign nephrosclerosis that is seen as a reduction in kidney size and
smoothness due to fibroelastic hyperplasia (duplication of elastic lamina
in the renal arteries) that causes proteinuria and reduced GFR (esp. in
diabetes and blacks)
o Hypertensive heart disease that can cause:
§ LVH
§ Atrial fibrillation due to left atrial enlargement that produces disorganized electrical impulses usually originating in the roots of
the pulmonary veins
§ Decompenstated cardiac failure
o Aortic dissection as pressure leads to a tear in the tunica intima that allowed blood to flow into the tunica media expand to create a
new route – this can travel distally or back into the pericardial space to cause tamponade
o Saccular “Berry” aneurysms of cerebral circulation that can lead to subarachnoid haemorrhage
Michael Grant
lOMoARcPSD|4927727

• Treatment:
Pulmonary hypertension is an increase of blood pressure in the pulmonary artery, pulmonary vein, or pulmonary
capillaries leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms.
It can be either:
• Primary – unknown cause
• Secondary:
o Left ventricular failure
o Mitral stenosis
o Chronic bronchitis – hypoxia causes vasoconstriction, increasing pressure
o COPD – reduction in pulmonary tissue and accompanying vascular bed leads to an increase
in resistance and, thus, pressure
o Pulmonary embolus
• Complications:
o Cor Pulmonale - enlargement and failure of the right ventricle of the heart as a response to increased
vascular resistance
Atrial fibrillation is a chaotic, irregular atrial rhythm at 300–600bpm; the AV node responds intermittently, hence an irregular ventricular rate.
• Cardiac output drops by 10–20% as the ventricles aren’t primed reliably by the atria.
• AF is common in the elderly (≤9%).
• The main risk is embolic stroke. Warfarin reduces this to 1%/yr from 4%. So, do an ECG on everyone with an irregular pulse (±24h ECG if
dizzy, faints, palpitations, etc.)
• It can be classified as:
o Paroxysmal recurrent episodes that stop on their own in less than 7 days
o Persistent recurrent episodes that last more than 7 days
o Permanent an ongoing long-term episode
• Causes:
o Pulmonary embolism, pulmonary disease, pneumonia, post-operative
o Ischemic heart disease, idiopathic (“lone atrial fibrillation”)
o Rheumatic valvular disease (mitral stenosis or regurgitation)
o Anemia, alcohol (“holiday heart syndrome” after binge drinking), age, autonomic tone (vagal atrial fibrillation)
o Thyroid disease (hyperthyroidism)
o Elevated blood pressure (hypertension), electrocution
PIRATES treasure is RARE
o Sleep apnea, sepsis, surgery
• Treatment consists of 4 aspects:
o Rate control
§ Beta-blocker (particularly bisoprolol) or rate-limiting Ca2+ blocker (Verapimil or Diltiazem) are 1st choice. If this fails, add
digoxin, then consider amiodarone
o Aetiology – find and treat (see causes above)
o Rhythm control – amiodarone or DC cardioversion
§ Chronic AF:
• Cardioversion is chosen, do echo 1st; pre-treat for ≥4wks with sotalol or amiodarone if there is increased risk of
cardioversion failure (past failure, or past recurrence)
Michael Grant
lOMoARcPSD|4927727

o Pharmacological cardioversion: flecainide (powerful negative inotrope regulating the flow of sodium in the heart,
causing prolongation of the cardiac action potential) in is 1st choice if no structural heart disease (IV amiodarone if
structural heart disease).
o If >48h, ensure ≥3wks of therapeutic
anticoagulation before elective cardioversion;
NB trans-oesophageal-guided cardioversion is
also an option here
• Invasive: AV node ablation, maze procedure, pacing,
and pulmonary vein ablation are options to ask about
§ Paroxysmal AF: ‘pill in the pocket’ (eg sotalol or flecainide
PRN) may be tried if: infrequent AF, BP >100mmHg systolic,
no past LV dysfunction.
o Embolic prophylaxis – see ESC guidelines below
§ Aspirin can be used in warfarin not tolerated and very low
risk of thrombus
§ NOACs – e.g. apixaban – if CHA2DS2VASc is 2 or greater
§ Warfarin can be considered in place of NOAC generally but
is the only option for those with mechanical valves or
mitral stenosis
Acute AF (<48h) require treatment immediately:

• If very ill or haemodynamically unstable:
o Emergency cardioversion; if unavailable try IV amiodarone - do not delay treatment in order to start anti-coagulation.
o Cardioversion regimen: ฀O2 ฀ITU/CCU ฀GA or IV sedation, monophasic > 200J > 360J > 360J (biphasic; 200J).
§ Relapses back into AF are common. Drug cardioversion is often preferred: amiodarone IVI (5mg/kg over 1h then ~900mg over
24h via a central line)
• Otheriwise:
o Treat associated illnesses (eg MI, pneumonia).
o Control ventricular rate: 1st-line verapamil (40–120mg/8h PO) or bisoprolol (2.5–5.0mg/d PO). 2nd-line: digoxin or amiodarone.
o Start full anticoagulation with LMWH, to keep options open for cardioversion even if the 48h time limit is running out
§ If the 48h period has elapsed, cardioversion is OK if transoesophageal echo thrombus-free.
Atrial flutter usually associated with a fast heart rate or tachycardia (beats over
100 per minute) and falls into the category of supra-ventricular tachycardias
• While this rhythm occurs most often in individuals with cardiovascular
disease (e.g. hypertension, coronary artery disease, and cardiomyopathy)
and diabetes mellitus, it may occur spontaneously in people with otherwise
normal hearts
• It is typically not a stable rhythm, and frequently degenerates into atrial
fibrillation (AF).
• ECG: continuous atrial depolarization (eg ~300/min, but very variable) produces a sawtooth baseline ± 2 : 1 AV block (as if SVT at, eg
150bpm)
• Carotid sinus massage and IV adenosine transiently block the AV node and may unmask flutter waves
• Treatment: Cardioversion may be indicated but anticoagulate before.
o Anti-AF drugs may not work—but consider amiodarone to restore sinus rhythm, and amiodarone or sotalol to maintain it
Michael Grant
lOMoARcPSD|4927727

o Cavo-tricuspid isthmus (body of fibrous tissue in the lower right atrium, between the inferior vena cava, and the tricuspid valve. It is a
target for ablation for treating atrial flutter.
Valve disease typically can take one of 3 forms:

• Stenosis – thickened and/or calcified valves
• Incompetence/regurgitation – leaky valves allowing backflow
• Mixed mitral valve disease can show signs of both
Causes:
• Age-related calcification
• Rheumatic fever
• Myxomatous valve changes (connective tissue becomes floppy due to accumulation of dermatan sulfate,
a glycosaminoglycan, within the connective tissue)
• Congenitial defects (including bicuspid valves)
• Infective endocarditis
• MI causing damage to chorda or papillary muscle
Rheumatic fever is caused in children by a pharyngeal infection by the Group A, Beta-haemolytic Strep.
Pyogenes. The symptoms of the fever present 2-6 weeks after the initial infection in the susceptible 2% of the
population. The infection is thought to expose T-Cells to M protein in the cell wall of S. Pyogenes which is
similar enough to valve tissue to cause a cross-reaction with the anti-bodies produced, leading to:
• Fibrinous pericarditis – causing a “pleural rub” (squeaking/grating sound on auscultation)
• Myocardial “aschoff” body – myocarditis seen as central core of collagen with a border of aschoff giant
cells and anitschkow cells (caterpillar shaped chromatin)
• Diagnostic criteria: Revised Jones Criteria; Evidence of recent Strep pyogenes infection (throat culture,
streptococcal antigen test
o Major: Carditis, polyarthritis, Sydenham’s chorea (rapid, uncoordinated jerking movements primarily affecting the face, hands and
feet – may last for months), erythema marginatum (pink rings on the torso and extensor surfaces of the limbs), subcutaneous nodules
o Minor: Fever, rasied CRP, ECG changes (prolonged PR interval)
• Management: Antibiotic treatment in patients who present with acute rheumatic fever (ARF) is necessary irrespective of the throat culture
result, the rest of management is conservative – Salicylates and bed rest
• Relevant to valve disease as it can present years later as valvular stenosis, most commonly involving the mitral valve. These patients are
prone to infective endocarditis and stroke.
Aortic stenosis is brought about by an inflammatory process due to mechanical damage to the
endothelium (leading to the deposition of LDLs). This triggers a cascade of aortic sclerosis, fibrosis,
increased stiffness followed by LVH.
• Causes: Calcific degeneration with age, congential (bicuspid valve – 3% of population, William’s
Syndrome), Rheumatic fever
• Classic triad: Syncope, Dyspnoea & Angina
• Signs:
o Slow-rising pulse (small pulse pressure)
o Praecordial systolic thrill +/- heave
o Ejection systolic murmur that radiates to the carotids
o Decreased intensity of A2 – usually sign of serve disease
• Differential diagnosis: Hypertrophic cardiomyopathy, Aortic sclerosis (is
senile degeneration of the valve. There is an ejection systolic murmur, no
carotid radiation, and normal pulse (character and volume) and S2)
• Complications: Sudden death, infective endocarditis
• Investigations:
o ECG – look for signs of LVH (Tall R waves [S in V1 or V2 + R in V5 or V6 (whichever is
larger) ≥ 35 mm (≥ 7 large squares)] & T inversion
o Echo – morphology, Doppler pressure gradient, extent of LVH; scoring critera for
severity (table to right)
o Cardiac catheterisation – direct pressure measurement
• Treatment:
o Medical – no specific treatment other than maintenance of good dental hygiene
o Surgery - prompt valve replacement is usually recommended:
§ If the patient is not medically fit for surgery, percutaneous
valvuloplasty/replacement (TAVI = transcatheter aortic valve implantation) may
be attempted
§ Open surgery – artificial valves (greater longevity, but lifelong warfarin) or
porcine (no warfarin, but shorter lifespan)
Michael Grant
lOMoARcPSD|4927727

Aortic regurgitation is the abnormal backflow of blood into the LV when aortic pressure > LV pressure, leading to increased stroke volume
and LVH. As pathology continues, LV will eventually decompensate and dilate.
• Causes:
o Aortic root disease (most common cause) can be caused by inflammatory
conditions and cause an opening between the cusps allowing for backflow
§ Hypertension
§ Aortic dissection +/- Marfan’s/Ehlers-Danlos/Pseudoxanthoma
elasticum (mineralization of elastic fibers > premature atherosclerosis)
§ Aortitis (e.g. Giant cell aortitis)
§ Takayasu's disease - a form of large vessel
granulomatous vasculitis with massive intimal Rhumatic
fibrosis and vascular narrowing, commonly in
Asian women Endocarditis
o Valve disease Ank. Spond/Aortic Dissection
§ Bicuspid aortic valve Luetic heart disease (Tertiary syphilius)
§ Rheumatic fever
§ Infective endocarditis Marfan’s
§ Ank. Spond. +/- Psoriatic arthropathy
• Signs:
o Bounding/Corrigan’s pulse due to the wide pulse pressure that will collapse
upon raising arm – as blood is poured back by gravity through faulty valve –
creating a knocking sensation on your arm
o Early diastolic murmur (loudest at LLSE)
o Laterally displaced apex
o Prominent carotid (Corrigan’s sign - powerful pulsation of the carotid arteries
causing ear movement and/or head nodding)
o de Musset’s sign: head nodding with each heart beat
o Quincke’s sign: capillary pulsations in nail beds
o Duroziez’s sign: compressing femoral artery 2cm proximal to stethoscope gives a
systolic murmur; 2cm distal, gives diastolic as blood flows backwards
o Traube’s sign: ‘pistol shot’ sound: over femoral arteries; an Austin Flint
murmur
• Tests:
o ECG: LVH - Sokolov-Lyon criteria; (S wave in V1) + (tallest R wave in V5-V6)
> 35 mm
o CXR: cardiomegaly; dilated ascending aorta; pulmonary oedema.
o Echocardiography is diagnostic
o Cardiac catheterization to assess: severity; anatomy of aortic root; LV
function; CAD
• Treatment
o ACE-i are helpful
o Same as AS but decision for surgery goes by the 55s rule:
§ Ejection fraction <55%
§ End-systolic dimension <55mm
Mitral stenosis is restricted almost exclusively to older patients as rheumatic fever

is the only common cause; the pathophysiology involves increases in mitral
resistance > L atrial dilation > Pulmonary hypertension > RV overload > RVH
• Causes:
o Rheumatic heart disease
o Amyloidosis from RA or SLE
o Congenital
o Rare: mucopolysaccharidoses, endocardial
fibroelastosis, malignant carcinoid, prosthetic
valve.
• Signs:
o Pulmonary oedema:
§ SOD
§ Orthopnoea & PND
§ Pink sputum
§ Crepitations
o Wheeze
o Palpitations (atrial fib.)
o Low volume pulse
o A tapping, non-displaced, apex beat (palpable S1)
Michael Grant
lOMoARcPSD|4927727

o Auscultation: loud S1; opening snap; mid-diastolic murmur (best
in expiration, with patient on left side)
o The more severe the stenosis, the longer the diastolic murmur,
and the closer the opening snap is to S2.
o Orther’s syndrome (cardiovocal syndrome and refers to recurrent
laryngeal nerve palsy from cardiovascular disease)
§ Dysphasia can also occur from pressure from large LA
o Mallar flush on cheeks due to decreased cardiac output
§ Important to differentiate this from butterfly rash in SLE, which
also can cause MS
• Tests:
o ECG: AF; P-mitrale (broad, notched (bifid) P waves in lead II is a
sign of left atrial enlargement) if in sinus rhythm; RVH – seen as
dominant R wave in V1 [> 7mm tall or R/S ratio > 1], Dominant S
wave in V5 or V6 (> 7mm deep or R/S ratio < 1), QRS duration <
120ms (i.e. changes not due to RBBB); and progressive right
deviation.
o CXR: left atrial enlargement (double shadow in right cardiac
silhouette); pulmonary oedema; mitral valve calcification
o Echocardiography is diagnostic - significant stenosis exists if the valve orifice is <1cm2/m2 body surface area.
§ Normal mitral area of 4-6cm2 with no pressure gradient; Mild MS - <2cm and <5mmHg; Severe MS at <1cm and >19mmHg
o Indications for cardiac catheterization: previous valvotomy; signs of other valve disease
• Management:
o Dental hygiene +/- ABx prophylaxis
o If in AF, rate control is crucial; anti-coagulate with warfarin.
o Loop diuretics and ACE-I will decrease preload and pulmonary venous congestion and oedema
§ If this fails to control symptoms, balloon valvuloplasty (if pliable, non-calcified valve), or open mitral valvotomy or replacement.
• Complications:
o A Fib
o Pulmonary hypertension
o Emboli
o RVH
o Tricuspid regurgitation
Mitral regurgitation is much more common that

mitral stenosis. Backflow into the L atrium It has
many causes:
o Chronic: LVH (causing annular
dilatation), myxomatous degeneration
(increased GAGs and, thus, water
content), annular calcification (elderly),
rheumatic fever, mitral valve prolapse
(most common valvular abnormality);
connective tissue disorders (Ehlers–Danlos, Marfan’s); cardiomyopathy;
o Acute: Infective endocarditis, ruptured chordae tendinae; papillary muscle
dysfunction/rupture; trauma
• Symptoms: Dyspnoea; fatigue; palpitations; infective endocarditis.
• Signs: AF; displaced, hyperdynamic apex from cardiomegaly; RV heave; soft S1; split
S2; loud P2 – The “ken-tuck-y” beat – (pulmonary hypertension) pansystolic murmur
at apex radiating to axilla.
o Severity: The more severe, the larger the left ventricle.
• Tests:
o ECG: AF ± P-mitrale if in sinus rhythm (increased L atrial size); LVH
o CXR: big LA & LV; mitral valve calcification; pulmonary oedema.
o Echocardiogram to assess LV function and aetiology (trans-oesophageal to assess severity and suitability for repair rather than
replacement). Doppler echo to assess size and site of regurgitant jet.
o Cardiac catheterization to confirm diagnosis, exclude other valve disease, assess coronary artery disease.
• Management:
o Control rate if fast AF.
Michael Grant
lOMoARcPSD|4927727

o Anticoagulate if: AF; history of embolism; prosthetic valve; additional
mitral stenosis.
o Diuretics improve symptoms. Surgery for deteriorating symptoms; aim
to repair or replace the valve before LV irreversibly impaired; can
lead to systolic dysfunction and, eventually, cardiogenic shock
o SBE/IE prophylaxis for GI/GU infected procedures.
• Complications:
o A. Fib
o LV dilation
o Infective endocarditis
o Arrhythmias
o Pulmonary oedema
Infective endocarditis occurs during endothelia injury healing, in which a

thrombus forms and allows bacteria to adhere to fibrin. It is typically classified by:
• Status: active/unactive
• Microbiology: causative pathogen
• Valve nature: Native/Mechanical/Porcine/Bovine/Cadaveric
• Location: Aorta/Mitral/Pulmonary/Tricuspid
e.g. Active Staph Aureus endocarditis of the native aortic valve
Pathogenesis: It typically occurs on a valve but can occasionally
affect the walls of the heart, especially if there is a congenital defect.
• Bacteria settles on thrombus to form a vegetation
• Vegetation are made up of pathogenic organism, platelets &
fibrin and inflammatory cells
• The inflammation and repair can lead to reduced valve function
• Most common causative organism is S. Aureus; but other
common causes can be determined based on their likely
origin:
o Strept. Viridans, Strept. Bovis or enterococci are common
dental sources (bacteria introduced to bloodstream
during chewing)
o Staph. Epidermidis after valve replacement, surgery or
long lines.
o Unusual causes are: HACEK Gram –ve bacteria -
Haemophilus – Actinobacillus – Cardiobacterium –
Eikenella – Kingella)
o Can also be caused by SLE plaques: Libman–Sacks
endocarditis
Signs:
• Septic: Fever, rigors, night sweats, malaise, weight loss, anaemia, splenomegaly, and clubbing
• Cardiac: Murmur (occasionally Seagull/Cooing murmur, with ruptured chordea acting like string of musical instrument), prolonged PR
(from absess in aortic root)
• Immune complex: Vasculitis (of any vessel), Microscopic haematuria is common; via glomerulonephritis and acute renal failure, Roth
spots (boat-shaped retinal haemorrhage with pale centre); splinter haemorrhages; Osler’s nodes (painful pulp infarcts in fingers/toes)
• Embolic: mycotic abscesses (and aneurysms) in the relevant organ, eg Left-sided - brain, heart, kidney, spleen, gut (or lung if right-sided
IE) or skin: termed Janeway lesions
Risk factors: FROM JANE:

Fever
• Valve disease/replacement or any congenital defects
Roth's spots
• Hypertrophic cardiomyopathy Osler's nodes
• Bacteraemia risks - IV Narcotics, DM, dental illness/poor hygiene Murmur
• Catheters/lines Janeway lesions
Anemia
Complications: Nail hemorrhage
• Destruction of tissue; valve, chordea (splinter hemorrhages)
• Emboli (from vegatations) Emboli
• Heart block (aortic root abscess)
• Emboli obstruction (PE, stroke, bowel, renal infarcts – important to monitor U&Es)
Diagnosis: (Duke’s criteria – box to right)

• Blood cultures very important – 3 sets from DIFFERENT sites, BEFORE ABx
o Incubate for 7 days
Michael Grant
lOMoARcPSD|4927727

• Transthoracic and Transoesophageal echos are useful
o Look for motile mass on endocardium
Rx: Liaise early with microbiologist and cardiologists, to guide ABx per trust guidelines; but
consider surgery if: heart failure, valvular obstruction; repeated emboli; fungal endocarditis;
persistent bacteraemia; myocardial abscess; unstable infected prosthetic valve.
Recommendations: Give clear information about prevention, including:

• The benefits and risks of antibiotic prophylaxis (no good evidence).
• The importance of maintaining good oral health.
• Symptoms that may indicate IE and when to seek expert advice.
• The risks of invasive procedures, including piercing or tattooing.
Cardiac failure is the inability of the heart to pump blood to meet the metabolic demands of
tissues.
• Also refered to as congestive heart failure, it can be considered as:
o Forward failure with decreased output
o Backward failure with damming of blood in the venous system
o Mixed
• Cardiac adaption to failure:
o Frank-Starling mechanism – increased preload causes a stretch of myofibres,
increasing the force of contraction and, thus, stroke volume
o Myocardial structural changes – hypertrophy (usually of LV)
o Activation of neurohumeral systems – RAAS, atrial naturetic factor, secretion of
noradrenaline from cardial nerve (increasing contractility)
• Left-sided failure:
o Causes: ischaemic heart disease, hypertension, aortic/mitral valve disease,
cardiomyopathy
o Signs/Symptoms:
§ Evidence of ischaemia in heart (i.e. immotile sections, narrowed vessels, ECG
changes)
§ Pulmonary oedema (pink, frothy sputum and increased vessel markings or
batwing on CXR)
§ Renal hypoperfusion occurs and causes the activation of the RAAS system,
thus increasing salt and H2O retention, and BP – leading to a prerenal
renal failure with azotaemia (high levels of nitrogen compounds – like
urea and creatinine – in the blood) from reduced filtering
§ Ischaemic hypoxic encephalopathy causing coma and death if LSF
severe
• Right-sided failure:
o Causes: Left-sided failure, chronic lung disease (cor pulonale – increased
pulmonary vasculature resistance)
o Liver and portal hypertension
§ Congestive hepatomegaly (nutmeg liver; chronic passive congestion
is "speckled" like a grated nutmeg kernel; the dark spots represent
the dilated and congested hepatic venules)
§ Bowel wall oedema (leading to malabsorption)
o Splenomegaly
o Pleural and Pericardial effusion
o Peripheral oedema
• Treatment see ECS tables to right
Hypertrophic cardiomyopathy is the presence of inappropriate ventricular

hypertrophy – typically asymmetric – without an underlying, identified causes that is
the most common cause of sudden cardiac death in the young.
• It is produced by autosomal dominant mutations in the genes coding cardiac
sarcomeric proteins – typically thsie in the beta-myosin heavy chain and
myocin-binding protein C – but 50% are de novo mutations
• There are variations based on the locations and type of hypertrophy – but the
most common is asymmetric ant. wall & septum causing an obstruction to the flow and
eventually leading to diastolic dysfunction, as ventricle too stiff to relax and increase internal
volume
• Increased risk of endocarditis
• Symptoms: Sudden death, angina, dyspnoea, palpitation, syncope
o Mimics the triad of AS: syncope, SOB and angina
• Signs: Ejection systolic murmur, occasionally has S4, can lead to MR, but may have
NORMAL EXAMINATION
• Investigations:
o ECG: LVH, LBBB (septal mass compresses branch), Giant T wave inversion
Michael Grant
lOMoARcPSD|4927727

o Echo: asymmetrical septal hypertrophy; small LV cavity with hypercontractile posterior wall; midsystolic closure of aortic valve; systolic
anterior movement of mitral valve.
o Cardiac catheterization: may provoke VT. It helps assess: severity of gradient; coronary artery disease or mitral regurgitation
o Exercise test ± Holter monitor to risk stratify
o Family screening is important in first degree relatives with DNA analysis and follow-up, making sure to discourage intensive exercise
• Treatment:
o Medical: Aim to improve diastolic function – Beta-blockers, verapamil, disopyramide (Antiarrhythmic with strong –ve inotropy)
o Surgery:
§ Open surgical myectomy – good results and allows for concurrent treatment of valve pathology, although is risky in the >65 y.o.
§ Non-surgical alcohol ablation – involves the insertion of a catheter into the first septal artery to induce a controlled infarction by
introducing alcohol; it has a higher rate of complications but is less invasive
§ Duel chamber pacing – pacemaker targeted at apices to increase output
§ Implantable cardiac defibullator – effective in high risk individuals due to chance of VT
Myocarditis is an inflammation of the myocardium of the heart.

• Causes:
o Viral:
§ Cardio-selective: Coxsackie B, echo, adenoviruses (in children)
§ Non-cardio-selective: influenza, varicella zoster
o Bacterial: Clostridia, diphtheria, TB, meningococcus, mycoplasma, brucellosis,
psittacosis
o Spirochaetes: leptospirosis, syphilis, Lyme
o Protozoa: Chagas’
o Ionising radiation
o Drugs: ethanol (alcohol directly damages myocytes), clozapine,
cyclophosphamide, herceptin, penicillin, chloramphenicol, sulfonamides,
methyldopa, spironolactone, phenytoin, carbamazepine
• Symptoms & signs: Fatigue, dyspnoea, chest pain, fever, palpitations, tachycardia,
soft S1, S4 gallop
• Tests: ECG: ST elevation or depression, T wave inversion, atrial arrhythmias, transient
AV block. In proper clinical setting (and absence of MI) +ve troponin I or T confirms
the diagnosis
• Treatment: Supportive
Pericarditis is an inflammation involving the visceral and/or pariental pericardium –

typically producing a pericardial effusion.
• Causes:
o Infection (e.g. rheumatic fever, TB)
o Post-surgery
o Inflammatory: rheumatoid arthritis, scleroderma, polyarteritis nodosa, and SLE
o Post-MI and/or Dressler’s syndrome
o Paraneoplastic
o Uraemia (from CKD)
• Symptoms: high temperature (fever), chest pain (middle of the chest, sharp and stabbing, may spread to the neck and/or shoulders;
Typically, worse if you take a deep breath, swallow, cough, or lie down and better if you sit up or lean forward.
• Signs: saddle shaped ST elevation, pericardial effusion on ECHO (if severe, swinging heart sign)
• Classification:
o Serous – clear, straw coloured, high specific gravity (ratio of the density of a substance to the density of a reference substance at same
temperature/pressure – usually water) and protein
o Serofibrinous – “bread & butter” pericarditis, clumps of fibrin in fluid
o Purulent – if pus present
o Blood-stained – usually indicates malignancy
o Caseous – cheese-like substance due to fungi or mycobacteria (e.g. TB, Leprosy)
§ Constrictive pericarditis is a complication of caseous (and purulent) pericarditis as healing causes a type of fibrotic obliteration
leading to a thickened, fibrotic pericardium, limiting the heart's ability to function normally.
Aneurysms are defined as “a localised, permanent, abnormal

dilation of a blood vessel – that expands during systole”.
• True aneurysms are made up of normal vascular wall layers;
intima, media, adventitia
o Saccular & Fusiform/Diffuse are caused by
atherosclerosis and inflammatory disorders (e.g.aortitis)
and tend to affect the aorta and cerebral arteries
o Dissections are typically caused by non-inflammatory
conditions that affect the components of the media (e.g.
marfan’s) and affect the aorta and its’ main branches
o Microaneurysms are usually caused by hypertension and
diabetes; they can affect the cerebral and retinal arteries
o Mycotic are caused by infections or septic emboli and can affect any vessel
Michael Grant
lOMoARcPSD|4927727

• False are haematomas that lie along the side of a vessel, enveloped by thee
adventitia and communicate with the lumen via defect in the media
o Typically caused by trauma, especially iatrogenically in the femoral artery
post-angiography
Aortic dissection is a tear/ulceration of the aortic wall causing an intimal flap that
allows for the formation of a false lumen; more common in blacks and men. Blood
splits the aortic media with sudden tearing chest pain (± radiation to back). As the
dissection extends, branches of the aorta occlude sequentially leading to
hemiplegia (carotid artery), unequal arm pulses and BP or acute limb ischaemia,
paraplegia (anterior spinal artery), and anuria (renal arteries).
• Causes are many, but include:
o Atherosclerosis
o Hypertension
o Connective tissue disorders: Marfan’s, Ehlers-Danlos, Polycystic kidney
disease
o Coarctation - congenital condition whereby the aorta is narrow, usually in the
area where the ductus arteriosus
o Inflammatory: giant cell arteritis (causing aortitis), syphilis, RA
o Iatrogenic (from cardiac catheterisation)
o Toxic (cocaine, crystal meth)
• Presentation:
o Very sharp pain – usually felt between the scapulae and may move as the tear
continues
o Syncope +/- neurological signs (cerebral ischaemia)
o Dyspnoea
• Signs:
o Unequal pulses
o Early diastolic murmur from aortic regurg.
o End organ ischaemia (may be seen as decreased eGFR, bowel sounds, muscle
strength)
• Complications:
o Aortic regurg (may lead to acute heart failure)
o Acute coronary artery occlusion (may lead to MI)
o Cardiac tamponade via a reterograde dissection
o End organ ischaemia (esp. acute renal failure, ischaemic bowel, stroke)
o Perforation with massive haemorrhage +/- haemoptysis, haematemesis,
haemothorax
• Investigations:
o ECG & CXR: may show widened mediastinum
o Thoracic/oesophagus echo: doesn’t capture all of aorta
o CT
o MRI – best image modality by difficult if patient in distress
o Angiography – not very sensitive and invasive
• Classifications:
o Stanford A – involving the ascending aorta (70%)
o Stanford B – not involving the ascending component
• Management:
o Medical focuses on pain management and BP control:
§ Morphine
§ ICU referral
§ IV Beta-blocker:
• Keep systolic at ~100–110mmHg with
Labetalol or Esmolol (t1⁄2 is ultra-short) by IVI is
helpful
• Calcium-channel blockers may be used if beta-
blockers contraindicated
• Acute operative mortality: <25%.
o Surgery depends on Stanford type:
§ Stanford A – Aorta Dacron graph implant (Tube or
trouser – latter if iliac involvement)
§ Stanford B – can be managed medically unless there are signs of end organ ischaemia, then
percutaneous stenting over the area of intimal damage is indicated
Michael Grant
lOMoARcPSD|4927727

Endocrinology
Thyroid disease
The thyroid develops from the pharyngeal epithelium and descends the neck, endodermal invagination
of tongue at foramen caecum at week 4 of gestation descends anterior to hyoid and larynx, leaving a
thyroglossal duct in its’ wake that eventually degenerates – hence, rarely, there can be ectopic thyroid
Contribution from fifth pharyngeal pouch (ultimobranchial body - C cells) allows thyroid hormone
secretion by 12th week of gestation. Cervical sympathetic nerves influence the function and secretion of
the thyroid by their effect on the vessels supplying them. Thyrotophin releasing hormone (TRH – a
tripeptide) is released by the hypothalamus which triggers the production of TSH in the anterior pituitary
(and also prolactin). TSH levels vary through the day and trough at 2pm, usually they are 30%
during the hours of darkness, thus it is important to test at similar times. TSH acts on the thyroid to
release T4 thyroxine and lesser amounts of T3 triiodothyronine (5 times more potent, the
majority of which is produced by peripheral conversion from T4) which both bind to thyroxine
binding globulin, and form a negative feedback for the circuit. The unbound proportion is that
active component, which acts via nuclear receptors to increase cell metabolism and increase
catecholamine effects.
• Testing: more useful to use titres of free T3 and T4 as the total numbers are effected by the
amount of TBG; which is increased in pregnancy, oestrogen therapy (HRT/COC) and hepatitis,
and decreased in nephrotic syndrome (protein loss), chronic liver disease and acromegaly.
o TSH levels are useful to determine thyroid state – i.e. decreased in hyperthyroidism from
negative feedback, raised in hypo.
o Other tests include: thyroid autoantibodies (anti-thyroid peroxidase may be raised in

hashimoto’s or graves), TSH receptor antibody (raised in graves), Ultrasound
(distinguishes cystic, i.e. low risk, nodles from solid), Isotope scan (Technetium or
123
Iodine to assess uptake in lesions compared to background – neutral or “hot” lesions
tend to be benign)
• Hyperthyroidism seen clinically as thyrotoxicosis, is the excess of thyroid hormone causing
diarrhoea, weight loss, anxiety, palpitations, sweating, heat intolerance, emotional lability
and – rarely – even psychosis, alopecia and chorea.
o Signs: Tachycardia, AF, fine tremor, palmar erythema, thin hair, lid lag and retraction,
goitre, bruit
o Tests: suppressed TSH, with high T4/T3, mild normocytic anaemia, mild neutropenia
(in Graves’)
o Causes: Graves’ disease (accounts for 2/3 of cases, TSH receptor antibodies produced in
associated with mutation of HLA-DR3 and vitiligo, T1DM and Addison’s; produces smooth
thyroid enlargement), toxic multinodular goitre (elderly, iodine-deficient area - may be
retro- or substernal – palpate down), toxic adenoma (hot nodule arises from follicular
epithelium with intact capsule), ectopic thyroid (physiologic, metastatic or struma ovarii
[teratoma with thyroid tissue]), exogenous (drugs – especially amiodarone, iodine
excess), subacute de Quervain’s thyroiditis (post-viral, painful goitre), palpation, childbirth,
persistent Piriform sinus, HAART treatment
o Rx: give beta-blockers for rapid control of symptoms
§ Anti-thyroid medications – Titration (titration of Carbimazole [prevents thyroid
peroxidase from iodinating the tyrosine residues – risk of agranulocytosis, get urgent
FBC if signs of sepsis] at 20-40mg/day as guided by TFTs) or block and replace
(carbimazole + thyroxine simultaneously [less risk of iatrogenic hypothyroidism] –
maintain for 12-18 months for Graves’ then trial without; relapse may require
radioiodine or surgery
§ Radioiodine to kill off some thyroid tissue – most become hypo- after treatment. Be
careful in active hyper- as can lead to thyroid storm
§ Thyroidectomy: Carries a risk of damage to recurrent laryngeal nerve (hoarse voice)
and hypoparathyroidism. Patients may become hypothyroid.
o Complications: Complications Heart failure (thyrotoxic cardiomyopathy, especially if
elderly), angina, AF (seen in 10–25%: control hyperthyroidism and warfarinize)
osteoporosis, ophthalmopathy, gynaecomastia, Thyroid storm (see management to right)
Michael Grant
lOMoARcPSD|4927727

o Thyroid eye disease is seen in 25-50% of Graves’ disease, with the greatest risk coming from smoking. Retro-orbital inflammation
and lymphocyte infiltration results in swelling of the orbit leading to: afferent pupillary defect, eyes protrude beyond the orbit (look
from above in the same plane as the forehead); conjunctival oedema; corneal ulceration; papilloedema; loss of colour vision,
ophthalmoplegia (especially of upward gaze)
§ Diplopia may be managed with a Fresnel prism stuck and mild disease can be treated
symptomatically; however, severe disease with ophthalmoplegia may need high dose
steroids (methylprednisolone)
§ Rarely can cause Stiff person syndrome – Emotional or tactile stimuli cause spasms due to
antibodies to glutamic acid decarboxylase in any autoimmune disease; Rx: baclofen ±
IVIg
• Hypothyroidism is usually an insidious disease seen with an increase in serum thyroid-stimulating
hormone (TSH) concentration with normal serum fT4 and fT3 concentrations (subclinical
hypothyroidism), followed by a decrease in serum fT4, at which stage most patients have symptoms
and require treatment (overt hypothyroidism).
o Signs: BRADYCARDIC; reflexes relax slowly; ataxia (cerebellar); dry thin hair/skin;
yawning/drowsy/coma; cold hands ± Temp decrease; ascites ± non-pitting oedema (lids;
hands; feet) ± pericardial or pleural effusion; round puffy face/double chin/obese; defeated
demeanour; immobile ± ileus; CCF
o Tests: TSH up, T4 down (in rare secondary hypothyroidism: T4 low and TSH low or normal due
to lack from the pituitary). Cholesterol and triglyceride raised; macrocytosis
o Causes:
§ Primary autoimmune hypothyroidism:
• Primary atrophic hypothyroidism: ≈6:1 causing diffuse lymphocytic infiltration,
leading to atrophy and thus no goitre
• Hashimoto’s thyroiditis: Goitre due to lymphocytic and plasma cell infiltration
(usually women aged 60–70yrs) and can be hypothyroid or euthyroid; rarely initial
period of hyperthyroid (‘Hashitoxicosis’). Thyroid autoantib odies (anti-thyroid
peroxidase) titres are very high.
§ Other causes of primary hypothyroidism: iodine deficiency (biggest cause worldwide),
Post-thyroidectomy or radioiodine treatment, drug-induced (Antithyroid drugs,
amiodarone, lithium, iodine), Subacute thyroiditis (temporary hypothyroidism after
hyperthyroid phase)
§ Secondary hypothyroidism: Not enough TSH due to hypopituitarism; very rare.
o Treatment:
§ Healthy and young: Levothyroxine (T4), 50–100μg/24h PO; review at 12wks. Adjust
6 weekly by clinical state and to normalize but not suppress TSH (keep TSH
>0.5mU/L). Thyroxine’s t1⁄2 is ~7d, so wait ~4wks before checking TSH to see if a
dose change is right. Once normal, check TSH yearly. Enzyme inducers increases the
metabolism of levothyroxine.
§ Elderly or ischaemic heart disease: Start with 25μg/24h; and increase dose by
25μg/4wks according to TSH
o Amiodarone is an iodine-rich drug structurally like T4; 2% of users will get
significant thyroid problems from it. Hypothyroidism can be caused by toxicity
from iodine excess (T4 release is inhibited). Thyroidectomy may be needed if
amiodarone needed. T1⁄2 of amiodarone ≈ 80d, check TFTs 6-monthly.
o Myxoedema coma is seen mostly in elderly patients and is associated with a
mortality rate between 20% and 50%. Patients may be on treatment for
hypothyroidism or be previously undiagnosed, but infections, discontinuation of
thyroid supplements, sedative drugs and anything that impairs the respiratory
system - eg, pneumonia, cardiac failure and myocardial infarction.
§ Patients present with: A reduced level of consciousness, Seizures,
Hypothermia, Features of hypothyroidism; Metabolic disturbances are also
prominent, including hyponatraemia and hypoglycaemia.
§ Treatment: Intravenous levothyroxine is used - usually start with a loading dose and then a lower dose for maintenance on a
daily basis. Other treatments that have been used are liothyronine (T3) but this
can cause arrhythmias. Other therapy is usually supportive - eg, correct
metabolic disturbances, patient warming if hypothermic and treatment of
precipitating factors.
• Intravenous hydrocortisone is also required, as impaired adrenal function
is present in profound hypothyroidism (but send a random blood cortisol
first).
• Thyroid cancer is a cancer originating from follicular or parafollicular thyroid cells.
These cells give rise to both well-differentiated cancers – papillary thyroid cancer (PTC)
and follicular thyroid cancer (FTC) – and anaplastic thyroid cancer (ATC), whose anaplastic cells are poorly differentiated. The second cell
type, the C or parafollicular cell, produces the hormone calcitonin (acts to reduce blood Ca+ and oppose parathyroid hormone) and is
the cell of origin for medullary thyroid cancer (MTC)
Michael Grant
lOMoARcPSD|4927727

o Warning signs include: solid, solitary, “cold” (does not take up radioiodine) nodules –
especially in males, changes in voice
o Risk factors: ionising radiation (including previous radio-iodine therapy), autoimmune
thyroiditis (e.g. hashimoto’s), RET proto-oncogene mutation, male gender, FAP
(Gardner’s syn)
§ Activating mutations in RET proto-oncogene can cause multiple endocrine
neoplasia type 2 (MEN 2). There are three subtypes based on clinical presentation:
MEN 2A, MEN 2B, and familial medullary thyroid carcinoma
o Exclude causes of benign masses such as: Benign colloid nodule, simple cyst, focal
thyroiditis, follicular adenoma, Hürthle cell adenoma
o Papillary (60%) is a slow growing and asymptomatic, typically seen as multifocal
nodules often in younger patients. Seen using radionucleotide scan and FNA for
diagnosis. 10YS is around 98% and histological features include: columnar epithelium,
orphan annie nuclei (from the comic strip character with empty circled eyes) and
psammona bodies (laminar calcium deposits)
o Follicular (<25%) can present with nodules that are functional (associated with a worse prognosis), TSH sensitive (thyroxine post-op
to supress TSH) and occur in middle-age & spreads early via blood. Histologically, follicular structure with invasion of fibrous capsule
and lymph.
o Medullary (5% - 80:20 of sporadic:MEN) is a neuroendocrine tumour of the parafollicular C-cells and thus may secrete calcitonin
(can be used as marker) and, potentially, amyloid. Associated strongly with MEN2 and with a 5YS of
50%. Histologically; nests of tumour cells and amyloid plague. Palpable nodule
§ Perform a phaeochromocytoma screen pre-op.
o Anaplastic is a poorly differentiated and has a mortality approaching 100%. It is associated with a
loss of p53 and seen with a multinodular goitre. Histologically; spindle-like cells, Ultrasound
pleomorphism and mitotic figures.
o Thyroid lymphoma (<5% - 3:1, F:M) is a rare cancer than can be complication of
chronic inflammation of thyroiditis (e.g. Hashimoto’s) and typically of a B Multiple nodules Solitary nodule
lymphocyte origin. May present with stridor or dysphagia. No surgery is
indicated but chemo therapy is effective.
No dominant nodule Dominant nodule FNA
o Surgical options:
§ Hemithyroidectomy removes one side of the thyroid plus the
isthmus and pyramidal lobe – suitable for Recurrent cysts, Follicular
Discharge
lesion, Colloid nodule and < 1cm papillary carcinoma
§ Total thyroidectomy – suitable for Papillary carcinoma (with nodes), Follicular
carcinoma, Medullary carcinoma (with nodes), Multinodular goitre with compressive symptoms/cosmetic concerns
• If nodes involved then central nodal neck dissection indicated
§ Complications:
• Haematoma – bleed into thyroid bed, may compress vocal cords and/or trachea leading to resp. distress
o Wound must be opened immediately and drained
• Nerve damage:
o External Sup. LN - voice changes, loss of high-pitch phonation (subtle change – singers may be only Px to notice)
o Recurrent LN (unilateral) - hoarse, weak voice
o RLN (bilateral) - loss of phonation, vocal cords left in midline, stridor/resp.
distress + tracheostomy
• Hypocalcaemia
o Unusual in hemi- but can occur in 1-2% of total due to bruising of
parathyroid glands
§ F/U: Radioactive 131I at 6 weeks, Thyroxine replacement, Thyroid Function Tests,
Serial thyroglobulin/Calcitonin/CEA (after total, there should be no thyroglobulin
circulating – increase may mean recurrence; Calcitonin / CEA useful in medullary)
Parathyroid disorders
Parathyroid hormone (PTH) is normally secreted in response to low ionized Ca2+ levels, by 4
parathyroid glands situated posterior to the thyroid. The effects of PTH are:
• Osteoclast activity releasing Ca2+ and PO43– from bones; increased Ca2+ and decreased
PO43– reabsorption in the kidney; Increase in production of Active 1,25 dihydroxy-vitamin
D3
o These have the overall effect of increasing Ca2+ and reducing PO43–
Primary hyperparathyroidism
Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands themselves.
• Causes: ~80% solitary adenoma, ~20% hyperplasia of all glands, <0.5% parathyroid cancer
• Presentation: Often ‘asymptomatic’ with raised Ca2+ on routine tests
• Signs relate to the effects of PTH:
o Raised Ca: weak, tired, depressed, thirsty, dehydrated-but-polyuric; also renal stones,
abdominal pain, pancreatitis, and ulcers 
o Bone resorption: pain, fractures, osteopenia/osteoporosis (T scores -1 to -2.5 and <-2.5)
o Raised BP: esp. in those wit MEN1
• Tests:
Michael Grant
lOMoARcPSD|4927727

o Raised Ca2+ & PTH
§ Although PTH may be inappropriately normal - other causes of this: thiazides, lithium, familial, hypocalciuric
hypercalcaemia, tertiary hyperparathyroidism
§ Increased 24hr urinary Ca
o Reduced PO43– (unless in renal failure), increased alk phos from bone breakdown
o XR Imaging may show osteitis fibrosa cystica - subperiosteal erosions, cysts, or brown tumours (not a neoplasm;
cause be breakdown of bone from PTH and consist of fibrous tissue, woven bone and supporting vasculature but
no matrix) of phalanges ± acroosteolysis (resorption of the distal bony phalanges)
o DEXA scan
• Treatment:
o If mild: advise fluid intake to prevent stones; avoid thiazides and high intake of Ca2+ & vit D; f/u 6 monthly
o Excision:
§ Indicated: high serum or urinary Ca2+, bone disease, renal calculi,
§ Excision of the adenoma or of all 4 hyperplastic glands
prevents fractures and peptic ulcers
§ Pre-op US and MIBI scan may localize an adenoma
§ Complications: Hypoparathyroidism, recurrent laryngeal nerve
damage, symptomatic Ca2+ reduced (hungry bones syndrome -
rapid, profound, and prolonged hypocalcaemia associated with
hypophosphataemia and hypomagnesaemia, and is exacerbated
by suppressed parathyroid hormone (PTH) levels)
§ Recurrence: Cinacalcet (a ‘calcimimetic’) to increase sensitivity of
parathyroid cells to Ca2+, this lowering PTH secretion
• Secondary hyperparathyroidism
o Due to physiological (i.e. appropriate) secretion of parathyroid
hormone (PTH) by the parathyroid glands in response to
hypocalcemia; low Ca2+, high PTH
o Causes: low vit D intake, chronic renal failure.
o Treatment: Correct underlying causes, phosphate binders; vit D;
cinacalcet (if PTH high), consider parathyroidectomy if resistant
• Tertiary hyperparathyroidism
o Seen in patients with long-term secondary hyperparathyroidism,
which eventually leads to hyperplasia of the parathyroid glands and a
loss of response to calcium levels
o High Ca2+, very high PTH (inappropriately) and occurs after
prolonged secondary hyperparathyroidism, causing glands to act
autonomously having undergone hyperplastic or adenomatous
change
• Malignant hyperparathyroidism: Parathyroid-related protein (PTHrP) is
produced by some squamous cell lung cancers, breast and renal cell
carcinomas, which mimics PTH and it’s effects
Hypoparathyroidism
• Primary hypoparathyroidism is seen as PTH secretion is decreased due to gland
failure
o Causes: Autoimmune; congenital (Di George synd.)
o Tests: Low Ca2+, High/normal PO43–
o Signs: Those of hypocalcaemia, p692 ± autoimmune comorbidities
o Causes: Autoimmune; congenital (Di George synd., OHCS p642).
o Treatment: Ca2+ supplements + calcitriol (or synthetic PTH to prevents
hypercalciuria)
• Secondary hypoparathyroidism is caused by radiation, surgery (thyroidectomy,
parathyroidectomy), hypomagnesaemia (magnesium is required for PTH
secretion)
• Pseudohypoparathyroidism is due to a failure of target cell response to PTH
and it’s pathogenesis has been linked to dysfunctional G Proteins (in particular,
Gs alpha subunit coded by GNAS1 gene). The condition is extremely rare, with
an estimated overall prevalence of 7.2/1,000,000 or approximately 1/140000.
o Signs: Short metacarpals (esp. 4th and 5th), round face, short stature,
calcified basal ganglia
o Tests: low Ca2+, high PTH (appropriately high due to the low level of
calcium in the blood), high PO43-
o Treatment: Ca2+ supplements + calcitriol (or synthetic PTH to prevents
hypercalciuria)
• Pseudopseudohypoparathyroidism has the morphological features of
pseudohypoparathyroidism, but with normal biochemistry. The GNAS1
gene involved in both pseudohypoparathyroidism type 1a and
pseudopseudohypoparathyroidism is greatly affected by imprinting. When a
Michael Grant
lOMoARcPSD|4927727

father who has pseudohypoparathyroidism undergoes spermatogenesis, imprinting of the GNAS1 gene inactivates both copies of his
genes, including the defective one. The seemingly contradictory presentation of
symptoms can be explained by the fact that most tissues in the body (e.g., bone)
reactivate the GNAS1 copy, whereas the kidneys do not – thus the offspring have
the morphological features but not the biochemical changes.
Pituitary disorders
The pituitary is formed from a fusion of an up-growth of the tongue (Rathke’s
pouch/Adenohypohysis/Anterior pituitary) & a down-growth of the brain
(Neurohypohysis/Posterior pituitary).
• The anterior consists of 3 types of cells: 40% acidophils (produce somatotropin/GH and prolactin),
10% basophils (ACTH, FSH, LH & TSH) and 50% chromophobes (function unknow, some secrete
MSH)
• The posterior consists of non-myelinated axons and nerve endings of neurosecretory
neurons whose cell bodies lie in the hypothalamus
• Pituitary adenoma are almost always benign be can cause:
o Mass effect – esp. bitemporal hemiopia, also:
§ Raised ICP
§ Destruction of adjacent tissue – hypopituitarism, erosion through
floor of sella leading to CSF rhinorrhoea
o Hormone secretion – prolactin, HG, ACTH, etc. based on cell of origin:
§ Acidophil – GH – acromegaly
§ Basophil – ACTH – Cushing’s
§ Chromophobe/microadenoma – prolactin – hyperprolactinaemia
o Non-function – may cause hypopituitarism
• Craniopharyngioma is not strictly a pituitary tumour: it originates from Rathke’s
pouch so is situated between the pituitary and 3rd ventricle floor.
o They are rare, but are the commonest childhood intracranial tumour.
o Over 50% present in childhood with growth failure; adults may present with
amenorrhoea, reduced libido, hypothalamic symptoms (eg diabetes insipidus,
hyperphagia, sleep disturbance) or tumour mass effect.
o May present with bitemporal inferior quadrantanopia leading to bitemporal
hemianopsia
o Tests: CT/MRI (calcification in 50%, may also be seen on skull x-
ray).
o Treatment: Surgery ± post-op radiation; test pituitary function
o There may also be a Rathke's cleft cyst is a benign growth found
on the pituitary gland in the brain, specifically a fluid-filled cyst in
the posterior portion of the anterior pituitary gland
Hypopituitarism entails decreased secretion of anterior pituitary hormones.

They are affected in this order: growth hormone (GH), gonadotropins:
follicle-stimulating hormone (FSH) and luteinizing hormone (LH), prolactin
(PRL), thyroid-stimulating hormone (TSH), and adrenocorticotrophic
hormone (ACTH)
• Panhypopituitarism is deficiency of all anterior
hormones, usually caused by irradiation, surgery, or
pituitary tumour
• Causes arise at 3 levels:
o Hypothalmus - Kallman’s syndrome (seen with
anosmia, failure of the hypothalamus to release
GnRH at the appropriate time as a result of the
GnRH releasing neurones not migrating into the
correct location during embryonic development),
tumour, inflammation, infection (meningitis, TB),
ischaemia
o Pituitary stalk: Trauma, surgery, mass lesion
(craniopharyngioma, meningioma, carotid artery
aneurysm)
o Pituitary: Tumour, irradiation, inflammation,
autoimmunity (hypophysitis), infiltration
(haemochromatosis [accumulation of iron in pituitary –
affect sex hormones], amyloid, metastases), ischaemia
(pituitary apoplexy; DIC; Sheehan’s syndrome)
§ Piturary tumours can cause hypopituitarism by mass
effect, or by hormone secretion with reduced
secretion of other hormones
§ Pituitary apoplexy is rapid pituitary enlargement
from a bleed into a tumour may cause mass effects,
Michael Grant
lOMoARcPSD|4927727

cardiovascular collapse due to acute hypopituitarism, and death. Suspect if acute onset of headache, meningism,
ophthalmoplegia/visual field defect, especially if there is a known tumour; Rx: Urgent steroids (hydrocortisone 100mg IV)
and meticulous fluid balance ± cabergoline (dopamine agonist, if prolactinoma) ± surgery
§ Sheehan's syndrome is hypopituitarism caused by ischemic necrosis due to blood loss during and after childbirth
• Sign/Symptoms are dependent on what hormones are lacking:
o GH lack: Obesity, atherosclerosis, dry wrinkly skin, reduced strength/balance/cardiac output/osteoporosis and reduced glucose฀
o Gonadotropin (FSH; LH) lack: oligomenorrhoea/amenorrhoea (or ED in men), reduced fertility and libido, osteoporosis
o TSH lack: hypothyroidism
o Corticotropin lack: adrenal insufficiency/addison’s (but no pigmentation due to lack of ACTH)
• Tests:
o Basal tests: LH and FSH (low/normal), testosterone or oestradiol (low); TSH (low/normal), T4 (low); prolactin (may be increase from
loss of hypothalamic dopamine that normally inhibits its release), insulin-like growth factor-1 (IGF-1 used as a measure of GH axis),
cortisol (low)
§ Also do U&E (Low Na+ from dilution), low Hb (normochromic, normocytic)
o Dynamic tests:
§ Short Synacthen® test: ACTH followed be cortisol measure to assess the adrenal axis
§ Insulin tolerance test (ITT): IV insulin to induce hypoglycaemia, causing stress to increase cortisol and GH secretion. It is done
in the morning (water only taken from 22:00h the night before). Have 50% glucose and hydrocortisone to hand and IV access.
Glucose must fall below 2.2mmol/L and the patient should become symptomatic when cortisol and GH are taken
§ Arginine + GHRH test: GHRH and the amino acid arginine can stimulate the pituitary gland into releasing growth hormone (GH).
During a GHRH+Arg test, the levels of growth hormone released by the pituitary gland can be measured in the blood at
regular intervals
§ Glucagon stimulation test is alternative when ITT is contraindicated
o Imaging: MRI scan to look for a hypothalamic or pituitary lesion
• Treatment:
o Treatment of underlying cause (tumour, infection, etc.)
o Hormone replacement:
§ Hydrocortisone for 2° adrenal failure before other
hormones are given (if throxine given first – risk of
adrenal crisis)
§ Thyroxine if hypothyroid (but TSH is useless for
monitoring).
§ Hypogonadism (for symptoms and to prevent
osteoporosis); testosterone enanthate (+ estrogen if
premenopausal)
§ Gonadotropin therapy is needed to induce fertility
in both men and women
§ Growth hormone – tricky in over 25s (see box)
Pituitary tumours (almost always benign adenomas) account for 10% of intracranial tumours. They may be divided by size: a microadenoma is
a tumour <1cm across, and a macroadenoma is >1cm. There are 3 histological types:
• Chromophobe — 70%. Many are non-secretory, some cause hypopituitarism. Half produce PRL; a few produce ACTH or GH
• Acidophil — 15%. Secrete GH or PRL
• Basophil — 15%. Secrete ACTH
• Features of local pressure:
o Headache, visual defects (bitemporal hemianopia), palsy of cranial nerves III, IV, VI (pressure or invasion of the cavernous sinus)
o Diabetes insipidus (DI) ( more likely from hypothalamic disease)
o Disturbance of hypothalamic centres of T°, sleep, and appetite
o Erosion through floor of sella leading to CSF rhinorrhoea.
• Tests:
o MRI defines intra- and supra-sellar extension
o Visual fields
o Screening tests: PRL, IGF-1 (to measure effects of GH), ACTH,
cortisol, TFTS, LH/FSH, testosterone in men, short Synacthen® test
§ Glucose tolerance test if acromegaly suspected
§ Water deprivation test if DI is suspected
• Treatment:
o Start hormone replacement as needed - Ensure steroids are given
before levothyroxine, as thyroxine may precipitate an adrenal crisis
o Surgery: Most pituitary surgery is trans-sphenoidal, but if there is
supra-sellar extension, a trans-frontal approach may be used
§ For prolactinoma, usually a microadenoma (<1mm), the 1st-line
treatment is medical with a dopamine agonist (Bromocriptine)
§ Post-op: Retest pituitary function to assess replacement needs.
o Radiotherapy: (eg stereotactic) Good for residual or recurrent
adenomas
Michael Grant
lOMoARcPSD|4927727

Arcomegaly is due to increased secretion of GH (growth hormone)
from a pituitary tumour (99%) or hyperplasia, eg via ectopic GHRH
from a carcinoid tumour (associated with MEN1). GH stimulates
bone and soft tissue growth through increased secretion of
insulin-like growth factor-1 (IGF-1)
• Symptoms:
o Acroparaesthesia (akron=extremities); amenorrhoea;
decreased libido; headache;sweating; snoring; arthralgia;
backache; malocclusion (imperfect positioning of teeth
when close) and curly hair
o Sign see box to right – if acromegaly occurs before the
epipshyeal plates fuse then gigantism occurs
• Complications
o May present late with CCF or ketoacidosis
o Impaired glucose tolerance (~40%), DM (~15%).
o Vascular: high BP, left ventricular hypertrophy
(±dilatation/CCF), cardiomyopathy, arrhythmias
o Colon cancer risk
• Tests:
o High Glucose, Ca2+ and PO43– (latter from bone turnover)
o GH: Don’t rely on random GH as secretion is pulsatile and
during peaks acromegalic and normal levels overlap.
§ GH also up in: stress, sleep, puberty, and pregnancy.
§ Normally GH secretion is inhibited by high glucose,
and GH hardly detectable. In acromegaly GH release fails to suppress
§ If basal serum GH is >0.4μg/L (1.2mIU/L) and/or if IGF-I raised - an oral glucose tolerance test (OGTT) is needed
• If lowest GH value during OGTT is above 1μg/L (3mIU/L), acromegaly is confirmed
o MRI scan of pituitary fossa
• Treatment:
o Aim to correct (or prevent) tumour compression by excising the lesion, and to reduce GH and IGF-I levels
st
§ 1 Line: Trans-sphenoidal surgery
nd
§ 2 Line: If surgery fails to correct GH/IGF-I hypersecretion, try somatostatin analogues (octreotide)
rd
§ 3 Line: GH antagonist pegvisomant (recombinant GH analogue) is used if resistant or intolerant to SSA
• Prognosis may return to normal (any excess mortality is mostly vascular)
Diabetes insipidus is the passage of large

volumes (>3L/day) of dilute urine due to
impaired water resorption by the kidney,
because of reduced ADH secretion from the
posterior pituitary (cranial DI) or impaired
response of the kidney to ADH (nephrogenic
DI).
• Hypernatraemia and high plasma
osmolality), with a low urine osmolality
• Symptoms: Polyuria; polydipsia;
dehydration; symptoms of
hypernatraemia (lethargy, weakness, confusion, irritability, myoclonic jerks and seizures).
o Polydipsia can be uncontrollable and all-consuming
• Causes:
o Cranial DI:
§ Idiopathic (50%)
§ Congenital: defects in ADH gene, DIDMOAD (autosomal recessive
disorder: Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and
Deafness)
§ Tumour (may present with DI + hypopituitarism): craniopharyngioma,
metastases, pituitary tumour
§ Trauma: temporary if distal to pituitary stalk as proximal nerve
endings grow out to find capillaries in scar tissue and begin direct
secretion again
§ Hypophysectomy
§ Autoimmune hypophysitis
§ Infiltration: histiocytosis, sarcoidosis (nuerosarcoid will have increased
protein on LP)
§ Vascular: haemorrhage (Sheehan’s syndrome)
o Nephrogenic DI:
§ Inherited
§ Metabolic: low potassium, high calcium
§ Drugs: lithium, demeclocycline
§ Chronic renal disease
Michael Grant
lOMoARcPSD|4927727

• Tests:
o U&E, Ca2+, glucose (exclude DM), serum and urine osmolalities.
§ Urine can be concentrated to more than twice this concentration.
Significant DI is excluded if urine to plasma (U:P) osmolality ratio
is more than 2 : 1, provided plasma osmolality is no greater than
295mOsmol/kg. In DI, despite raised plasma osmolality, urine is
dilute with a U:P ratio <2
o Diagnosis The water deprivation test aims to test the ability of
kidneys to concentrate urine for diagnosis of DI
§ Primary polydipsia there may be dilutional hyponatraemia (with
risk of central pontine myelinolysis) —and as hyponatraemia may
itself cause mania, so avoid jumping to the conclusion of water
intoxication from psychogenic polydipsia
• Treatment:
o Cranial DI: Find the cause—MRI (head); test anterior pituitary function.
§ Give Desmopressin, a synthetic analogue of ADH (eg Desmomelt®
tablets)
o Nephrogenic: Treat the cause. If it persists, try bendroflumethiazide
5mg PO/24h.
§ NSAIDS lower urine volume and plasma Na+ (prostaglandins locally
inhibit the action of ADH)
• Emergency:
o IVI to keep up with urine output. If severe hypernatraemia, do not lower Na+ rapidly as this may cause cerebral oedema and brain
injury. If Na+ is ≥170, use 0.9% saline initially—this contains 150mmol/L of sodium.
Aim to reduce Na+ at a rate of less than 12mmol/L per day. Use of 0.45% saline can
be dangerous.
o Desmopressin 2μg IM (lasts 12–24h) may be used as a therapeutic trial
Addison’s disease also known as primary adrenal insufficiency, is a long-term endocrine

disorder in which the adrenal glands do not produce enough steroid hormones. Symptoms
generally come on slowly and may include abdominal pain, weakness, and weight loss.
• Features:
o Hypotension/ Postural hypotension
o Electrolyte disturbance
§ Hyponatraemia
§ Hyperkalaemia
§ Hypercalcaemia
o Fatigue/lethargy
o Gastro-intestinal upset
o Hyperpigmentation
• Causes:
o 80% are due to autoimmunity in the UK
o Other causes:
§ Infective:
• TB (commonest cause worldwide)
• Opportunistic infections in HIV (eg CMV,
Mycobacterium avium)
§ Adrenal haemorrhage:
• Waterhouse–Friderichsen syndrome
(haemorrhage into 1 or both adrenal glands
secondary to severe infection +/- DIC; esp.
Meningococcal)
• Others: antiphospholipid syndrome; SLE;
anticoagulants
§ Malignant: Adrenal metastases (eg from lung, breast,
renal cancer), lymphoma
o Secondary causes:
§ Commonest cause is long- term steroid therapy leading to suppression of the pituitary-adrenal axis
§ Rare: hypothalamic-pituitary disease leading to reduced ACTH production; differs as mineralocorticoid production remains
intact (angiotensin dependant), and there is no hyperpigmentation as low/normal ACTH
• Symptoms:
o Often diagnosed late: trim, tanned, tired, tearful ± weakness, anorexia, dizzy, faints, flu-like myalgias/arthralgias
o Mood: depression, psychosis, low self-esteem
o GI: nausea/vomiting, abdominal pain, diarrhoea/constipation
o Skin: Pigmented palmar creases & buccal mucosa (At high levels ACTH; cross-reacts with melanin receptors), vitiligo
o Critical deterioration: Shock (increased BP, tachycardia), high T°, coma.
• Tests:
o Low Na+& high K+ (decreased mineralocorticoid), low glucose (decreased cortisol), uraemia, high Ca2+, eosinophilia, anaemia
o Synacthen® test: Do plasma cortisol before and 1⁄2h after administration of synthetic ACTH – normal response: increased cortisol
Michael Grant
lOMoARcPSD|4927727

o ACTH: In Addison’s, 9AM ACTH is high (>300ng/L: inappropriately high) but is low in secondary causes of adrenal insufficiency from
negative feedback (i.e. exogenous steroids)
o 21-Hydroxylase adrenal autoantibodies: +ve in autoimmune disease in >80%
o Plasma renin & aldosterone: To assess mineralocortocoid status
o AXR/CXR: Any past TB, e.g. upper zone fibrosis or adrenal calcification
• Treatment:
o Replace steroids, and titrate until optimized:
§ ~15–25mg hydrocortisone daily, in 2–3 doses, eg 10mg on waking, 5mg lunchtime. Avoid giving late (may cause insomnia –
interferes with circadian rhythm)
§ Mineralocorticoids to correct postural hypotension, low Na+, high K+: fludrocortisone PO
§ If there is a poor response, suspect an associated autoimmune disease (check thyroid, do coeliac serology)
§ Steroid rules:
• Do not stop abruptly
• Alert any doctors/dentists as to your steroid use
• Card an alert card in your wallet or wear alert bracelet
• Add 5-10mg of hydrocortisone if planning exercise that day
• Double dose in febrile illness
• Use 100mg IM syringe of hydrocortisone if vomiting prevents PO intake – seek medical help
• Prognosis: adrenal crses and infections do causes excuse deaths; men lose 11 years from average expectancy while women only 3.
Hyperaldosteronism
Primary hyperaldosteronism is excess production of aldosterone, independent of the
renin–angiotensin-aldosterone system, causing high sodium and water retention, and low renin
release
• Consider if the following features: hypertension, hypokalaemia or alkalosis in someone not on
diuretics
• Symptoms:
o Often asymptomatic or signs of hypokalaemia (p688): weakness (even
quadriparesis), cramps, paraesthesiae, polyuria, polydipsia
o BP can be raised but not always
• Causes:
o Primary:
§ Conn’s syndrome accounts for ~2⁄3 of cases and is due to a solitary
aldosterone-producing adenoma
§ Around ~1⁄3 are due to bilateral adrenocortical hyperplasia
§ Rare causes: adrenal carcinoma or glucocorticoid-remediable
aldosteronism (GRA)
• In glucocorticoid-remediable aldosteronism the ACTH
regulatory element of the 11B-hydroxylase gene fuses to the
aldosterone synthase gene, increasing aldosterone
production and bringing it under the control of ACTH
o Secondary hyperaldosteronism due to a high renin occurs with
reduced renal perfusion, eg in renal artery stenosis, accelerated
hypertension, diuretics, CCF or hepatic failure.
o Bartter’s syndrome is a major cause of autosomal recessive salt
wasting—via a sodium and chloride leak in the loop of Henle due to
defective channel. Presents in childhood with failure to thrive, polyuria
and polydipsia. BP is normal.
§ Sodium loss leads to volume depletion, increasing renin and
aldosterone production – in turn leading to hypokalaemia and
metabolic alkalosis
§ Treatment: K+ replacement, NSAIDS (to inhibit prostaglandins), and ACE-i
• Treatment:
o Conn’s: Laparoscopic adrenalectomy, w/ spironolactone (25–100mg/24h PO) for 4wks pre-op controls BP and K+
o Hyperplasia: Treated medically w/ spironolactone, amiloride, or
eplerenone (a newer selective aldosterone receptor antagonist, which
doesn’t cause gynaecomastia)
o GRA: Dexamethasone 1mg/24h PO for 4wks to suppress ACTH
production, normalizes biochemistry but not always BP.
Phaeochromocytomas are rare catecholamine-producing tumours. They arise

from sympathetic paraganglia cells (=phaeochrome bodies), which are
collections of chromaffin cells (a.k.a. pheochromocytes, are neuroendocrine cells
found mostly in the medulla of the adrenal glands) however it is possible for
extra-adrenal tumours (paragangliomas); these are rarer, and often found by the
aortic bifurcation (the organs of Zuckerkandl)
• They roughly follow the 10% rule: 10% are malignant, 10% are extra-
adrenal, 10% are bilateral, and 10% are familial
Michael Grant
lOMoARcPSD|4927727

• Associations: ~90% are sporadic; 10% are part of hereditary cancer syndromes eg thyroid, MEN-2a and 2b, neurofibromatosis, von
Hippel–Lindau syndrome
• Classic triad: Episodic headache, sweating, and tachycardia
• Tests:
o Plasma level + 3 ≈ 24h urines for free metadrenaline and normetadrenaline (better than catecholamines and vanillylmandelic
acid) ± clonidine (a2 blocker) suppression test if borderline
o Localization: Abdominal CT/MRI, or meta-iodobenzylguanidine (MIBG—chromaffin-seeking isotope) scan
• Treatment:
o Surgery + alpha-blockade pre-op: phenoxybenzamine (a-blocker) is used before B-blocker to avoid crisis from unopposed ฀-
adrenergic stimulation
Cushing’s disease/syndrome
The adrenal cortex produces steroids:
1 Glucocorticoids (eg cortisol), which affect carbohydrate, lipid and protein metabolism
2 Mineralocorticoids, which control sodium and potassium balance (eg aldosterone)
3 Androgens, sex hormones which have weak effect until peripheral conversion to testosterone and dihydrotestosterone.
Corticotropin-releasing factor (CRF) from the hypothalamus stimulates ACTH secretion from the pituitary, which in turn stimulates cortisol
and androgen production by the adrenal cortex; while mineralocorticoids are primarily under the influence of angiotensin. Cortisol is excreted
as urinary free cortisol and various 17-oxogenic steroids
Cushing’s syndrome is the clinical state produced by chronic glucocorticoid

excess + loss of the normal feedback mechanisms of the hypothalamo–pituitary–
adrenal axis and loss of circadian rhythm of cortisol secretion (normally highest on
waking)
• The chief cause is oral steroids. Endogenous causes are rare: 80% are due to
increased ACTH; of these a pituitary adenoma (Cushing’s disease) is the
commonest cause
• Causes:
o ACTH-dependent causes:
§ Cushing’s disease is the term for bilateral adrenal hyperplasia from
ACTH-secreting pituitary adenoma (usually a microadenoma); low-
dose dexamethasone test leads to no change in plasma cortisol
§ Ectopic ACTH: Especially small cell lung cancer and carcinoid
tumours.
• Specific features: pigmentation (high ACTH), hypokalaemic
metabolic alkalosis (high cortisol leads to mineralocorticoid
activity), weight loss, hyperglycaemia;
• Classic features may be absent
§ Rarely: Ectopic CRF production—some thyroid (medullary) and
prostate cancers
o ACTH-independent causes (decreased ACTH from negative feedback -
dexamethasone test won’t suppress cortisol):
§ Iatrogenic: Pharmacological doses of steroids (common).
§ Adrenal adenoma/cancer (may cause abdo pain ± virilization in
women)
§ Adrenal nodular hyperplasia
§ Rarely:
• Carney complex (autosomal dominant conditions comprising myxomas
of the heart and skin, hyperpigmentation of the skin (lentiginosis), and
endocrine overactivity)
• McCune–Albright syndrome (GNAS1 mutation, as in
pseudohypoparathyroidism)
• Symptoms:
o Weight gain; mood change (depression, lethargy, irritability, psychosis);
proximal weakness; gonadal dysfunction (irregular menses; hirsutism;
erectile dysfunction); acne; recurrent Achilles tendon rupture; occasionally
virilisation
• Signs:
o Central obesity; plethoric, moon face; buffalo neck hump; supraclavicular fat
distribution; skin & muscle atrophy; bruises; purple abdominal striae;
osteoporosis; high BP; high glucose; infection-prone
• Tests:
o Dexamethasone suppression test (box to right)
o Don’t rely on imaging as non- functioning ‘incidentalomas’ occur in ~5% on
adrenal CT and ~10% on pituitary MRI
• Treatment:
o Iatrogenic: Stop medications if possible
o Cushing’s disease: surgical removal of pituitary adenoma (trans-sphenoidally) or bilateral
adrenalectomy if source unlocatable, or recurrence post-op
Michael Grant
lOMoARcPSD|4927727

§ Complication: Nelson’s syndrome seen with strong skin pigmentation due to very high levels of ACTH from an enlarging
pituitary tumour, as adrenalectomy removes –ve feedback; responds to pituitary radiation
o Adrenal adenoma/carcinoma: Adrenalectomy ‘cures’ adenomas but rarely cures cancer. Radiotherapy & adrenolytic drugs
(mitotane) follow if carcinoma.
o Ectopic ACTH (e.g. lung or carcinoid): Surgery if tumour is located and hasn’t spread
Diabetes mellitus is defined as a cgronic disorder of carbs,

fat and protein metabolism. DM results from lack or
reduced effectiveness of endogenous insulin.
Hyperglycaemia is one aspect of a far-reaching metabolic
derangement, which causes serious microvascular
(retinopathy, nephropathy, neuropathy) or macrovascular
problems: stroke, renovascular disease, limb ischaemia—
and above all heart disease So think of DM as a vascular
disease.
• Insulin physiology focuses on the beta cell of the islet
of langerhan’s in the tail of the pancreas:
o Stimulation of the GLUT-2 receptors on the
surface of these cells by circulating glucose leads
to release of insulin
o Insulin binds to insulin receptors throughout the body causing: upregulation of GLUT-4 transporters (increasing glucose uptake by
cells) and anabolic and lipogenic effects
• Type 1 DM is an absolte lack of insulin due to an autoimmune reaction to beta cells. This is a multi-factorial disease associated with
mutations in HLA DR3/4 (chromosome 6, DR4 also linked to RA) and environmental factors (potentially viral infection – esp. rubella,
coxsackie, measles)
o Usually adolescent onset but may occur at any age
o Latent autoimmune diabetes of adults (LADA) is a form of type 1 DM, with slower progression to insulin dependence in later life
• Type 2 DM is caused by decreased Insulin secretion ± increased insulin resistance and is associated with obesity, lack of exercise,
calorie and alcohol excess.
o Higher prevalence occurs in Asians, men, and the elderly (up to 18%)
o Most are over 40yrs at time of diagnsois, but teenagers are now getting type 2 DM
o 80% concordance in identical twins, indicating stronger genetic influence than in type 1 DM
o Typically progresses from a preliminary phase of impaired glucose tolerance (IGT) or impaired fasting glucose
o Impaired glucose tolerance (IGT) Fasting plasma glucose <7mmol/L and OGTT (oral glucose tolerance) 2h glucose ≥7.8mmol/L but
<11.1mmol/L
o Impaired fasting glucose (IFG) Fasting plasma glucose ≥ 6.1mmol/L but
<7mmol/L (WHO criteria) - Do an OGTT to exclude DM
• Other causes:
o Drugs: Steroids; anti-HIV drugs; newer antipsychotics; thiazides
o Pancreatic: pancreatitis; surgery (where >90% pancreas is removed – esp.
tail); trauma; pancreatic destruction (haemochromatosis, cystic fibrosis);
pancreatic cancer.
o Endocrine: Cushing’s disease; acromegaly; phaeochromocytoma;
hyperthyroidism; pregnancy
o Others: congenital lipodystrophy; glycogen storage diseases.
• How should I diagnose type 2 diabetes in an adult?
• Suspect type 2 diabetes in an adult who presents with:
o Persistent hyperglycaemia (HbA1c more than 48 mmol/mol [6.5%] or random plasma glucose more than 11 mmol/L) —
be aware that the characteristic features (thirst, polyuria, blurred vision, weight loss, recurrent infections, and tiredness) are
not usually severe and may be absent.
o Risk factors for type 2 diabetes (such as a strong family history, obesity, or Black or Asian family origin).
o Evidence of insulin resistance (for example acanthosis nigricans - brown to black, poorly defined, velvety
hyperpigmentation of the skin. It is usually found in body folds).
• Diabetes is usually diagnosed by an HbA1c of 48 mmol/mol (6.5%) or more. If the use of HbA1c is inappropriate (for example in
people with end-stage chronic kidney disease), type 2 diabetes is diagnosed by a fasting plasma glucose level of 7.0 mmol/L or
greater.
o In an asymptomatic person, the diagnosis of diabetes should never be based on a single measure; at least one
additional abnormal HbA1c or plasma glucose level is essential. If the second test results are normal, arrange regular review
of the person.
o Be aware that severe hyperglycaemia in people with an acute infection, trauma, or circulatory (other stress) may be
transitory and should not be regarded as diagnostic of diabetes.
• Type 2 diabetes is more likely in a person with:
o No additional features of type 1 diabetes (such as rapid onset, often in childhood, insulin dependence, or ketoacidosis)
o No features of monogenic diabetes or diabetes secondary to a pathological condition or disease, drug treatment, trauma,
or pancreatic surgery.
When to avoid HbA1c or interpret results with caution:
• HbA1c should not be used to diagnose diabetes mellitus in the following groups:
• Children and young people (younger than 18 years of age).
• Pregnant women or women who are two months postpartum.
Michael Grant
lOMoARcPSD|4927727

• People taking medication that may cause hyperglycaemia (for
example corticosteroids).
• People with acute pancreatic damage, including pancreatic surgery.
• People with end-stage chronic kidney disease
• People with HIV infection
• Treatment:
o General: Structured education programme, offer lifestyle advice (including
smoking cessation), start a statin, control BP, give foot-care advice; Advise
informing driving licence authority and not to drive if hypoglycaemic spells
o Type 1: Insulin (see box to right)
o Type 2: Different options, see BMJ guide
o Drug types:
§ Metformin is a biguanide drug that reduces hepatic glucose ouput, increases liver, muscle and fat sensitive to insulin, and
increases peripheral glucose uptake and utilisation; it also slow gastric motility, improving satiety and encouraging weight loss
• S/E: GI disturbance, lactic acidosis (caution in liver and renal disease; stop if <30 eGFR)
§ Sulfonylurea (eg gliclazide 40mg/d) increase insulin secretion form beta cells
• S/E: hypoglycaemia (monitor glucose); weight gain (so gliptins) below, are an alternative if BMI >35
§ Glitazone act to increase insulin sensitivity;
• S/E: hypoglycaemia, fractures, fluid retention, ?hepatotoxic (do LFT every 8wks for 1yr, stop if ALT up >3-fold), bladder
cancer risk
• CI: past or present CCF (fluid retention can lead to decompensation); osteoporosis; monitor weight, and stop if increasing
or oedema appears
§ Glucagon-like peptide (GLP) analogues or incretins are gut peptides that work by augmenting insulin release – there are 2
drug classes:
• GLP-1 analogues—exenatide 5μg SC bd 1⁄4h before meals (>6h apart; avoid if eGFR <30)
Michael Grant
lOMoARcPSD|4927727

o Increased risk of pancreatitis and potentially
pancreas/thyroid cancer
• DPP-4 inhibitors (dipeptidyl peptidase 4 breaks down GLP-1;
sitagliptin; vilagliptin)
o Hypos possible from increasing effect of endogenous
GLP-1, headache is main S/E, caution in renal disease
§ Alpha-glucosidase inhibitors (acarbose) inhibits the breakdown of
starch to sugar (an add-on drug, often disappointing!), 50mg
chewed at start of each meal. S/E: flatulence
§ Sodium glucose cotransporter 2 inhibitors (SGLT) inhibit the
action of are sodium-dependent glucose transport proteins – of
which, SGLT2 is the major cotransporter involved in glucose
reabsorption in the kidney
• SGLT2 inhibitors are called gliflozins and lead to a reduction in
blood glucose levels by reducing the renal threshold and
allowing glucose to pass into the urine at lower concentrations
• The gliflozins: canagliflozin, dapagliflozin, and empagliflozin may
lead to euglycemic ketoacidosis
• Other side effects of gliflozins include increased risk of (generally
mild) urinary tract infections, candidal vulvovaginitis
• CI: <45 eGFR
• Complications of DM can be divided into 2 broad categories according to their

pathogenesis:
§ Non-enzymatic glycosylation when glucose products become linked to proteins
• E.g. HbA1c, Advanced glycosylation end products (AGE) involving collagen
§ Intracellular hyperglycaemia as seen in the cells of the retina, kidney and nervous system as
these cells do not depend on insulin for uptake of glucose, thus in hyperglycaemia they take
on too much causing sorbitol accumulation (unused glucose is converted to sorbitol then to
fructose, which also accumulates, so it can be used In glycolysis) producing an osmotic
change, free radicals and decreased NO (resulting in reduced vasodilation); the culmination of
these is cell damage.
o By system:
§ Vascular system complications are linked to level of glycaemic control which bring about increased blood lipids (w/ reduced
HDLs), increased thromboxane A2 activity (increased thrombosis risk) and hyaline arteriolosclerosis (thickening of the walls of
arterioles by the deposits that appear as homogeneous pink hyaline materia). These can lead to:
• Accelerated atherosclerosis
• MI
• Gangrene (100x risk)
§ Renal system:
• Large vessel disease causing decreased renal perfusion in turn raising renin secretion and BP (ACE inhibition can be
protective)
• Diabetic microangiopathy produces a diffuse
thickening of the basement membrane by deposition
of glycogenated collagen
o Glomerulosclerosis caused by increased
mesangial matrix (basement membrane like
compound that supports the glomerular
capillaries with cells similar to smooth muscle and
macrophage cells) which decreases the filtration
through to bowman’s space. This thickening can
either be diffuse or nodular (Kimmelstiel-
wilson syndrome – diabetic nephropathy seen
with nephrotic syndrome with excessive filtration
of protein into the urine (proteinuria), high blood
pressure (hypertension), and progressively
impaired kidney function)
• Vascular lesions due to hyaline atherosclerosis comprises afferent and efferent vessels
• Pyelonephritis than can lead to necrotising papillitis
o Patients with diabetes mellitus are at greater risk of UTIs in general (glucose in urine and alterned macrophage
function) and their likelihood to ascend to cause acute pyelonephritis
Michael Grant
lOMoARcPSD|4927727

o Necrosis occurs with destruction of the papillae of the kidney, usually as a result of pyelonephritis. If the necrotic
tissue sloughs into the ureters, it may cause renal colic and obstruction
• Ocular
o Microangiopathy:
§ Cotton wool spots
§ Flame haemorrhages
o Blindness
o Cataract formation (due to altered osmolality)
o Glaucoma
• Neurological
o Peripheral neuropathy of the motor, sensory and autonomic nerves occurs by the hyalinisation of the small vessels
that accompany nerves, leading to neuronal ischaemia. This can be seen as:
§ Gastroparesis +/- diarrhoea/constipation
o Central neuropathy leads to cerebral haemorrhage/infarction
• Skin
o Recurrent infections
o Necrobiosis lipoidica (necrotising skin condition affecting the dermis and deep fatty layer that usually occurs in
patients with diabetes mellitus, frequently appears on the patient's shins, often on both legs – PUVA therapy may help)
o Granuloma annulare - reddish bumps on the skin arranged in a circle or ring (leucocytosis clogs capillaries leading to
granuloma)
o Vitiligo
Hypercalcaemia
SEE SURGERY NOTES
Hypocalcaemia
SEE SURGERY NOTES
Neurology (see neurosurgery lecture in surgery notes for remaining neurology topics)
Motor neurone disease
MND is a cluster of major degenerative diseases characterized by selective loss of neurons in motor cortex, cranial nerve nuclei, and anterior
horn cells (anterior horn is motor – “moving forward”); however, it is distinct from MS and polyneuropathies (no sensory loss or sphincter
disturbance) and also from MG (no eye involvement)
• Amyotrophic lateral sclerosis–frontotemporal dementia locus on 9p21 explain 87% of disease cases
• Cause is unknown but evidence points to possible aetiologies involving free radicals (long motor
neurons vulnerable to oxidative damage?), excess levels of the excitatory neurotransmitter
glutamate (decreased activity of the excitatory amino acid transporter - EAAT2) and possibly a
susceptibility to apoptosis pathways
• Be suspicious in >40yrs with stumbling spastic gait, foot-drop ± proximal myopathy, weak
grip (door-handles don’t turn) and shoulder abduction (hair-wash-ing is hard), or aspiration
pneumonia
o Look for UMN signs: spasticity, brisk reflexes, plantars; and LMN signs: wasting,
fasciculation of tongue, abdomen, back, thigh
o Is speech or swallowing affected (bulbar signs)?
o Frontotemporal dementia occurs in ~25%
• There is no specific lab test, so diagnosis based on Revised El Escorial diagnostic
criteria for ALS (see chart to right) after the exclusion of other causes using CNS imaging
and examination.
• There are 4 clinical patterns:
o ALS/amyotrophic lateral sclerosis (archetypal MND; 50%)
§ Loss of motor neurons in motor cortex and the anterior horn
§ UMN signs + LMN wasting/fasciculation
§ Worse prognosis if: bulbar onset, older age
§ The split hand sign: wasting of thenar with hypothenar spared
o Progressive bulbar palsy (10%) only affects cranial nerves IX–XII
in the medulla
§ Signs: flaccid, fasciculating tongue (like a sack of worms); jaw
jerk is normal or absent, speech is quiet, hoarse, or nasal
§ Causes: MND, Guillain–Barré, polio (affects ant. horn),
myasthenia gravis, syringobulbia (syrinxes, or fluid-filled
cavities, affect the brainstem), brainstem tumours, central
pontine myelinolysis (osmotic demyelination syndrome caused
by severe damage of the myelin sheath in the brainstem)
o Progressive muscular atrophy (10%) Anterior horn cell lesion
only, thus no UMN signs
§ Affects distal muscle groups before proximal
§ Better prognosis than ALS.
Michael Grant
lOMoARcPSD|4927727

o Primary lateral sclerosis involves a loss of Betz cells (giant pyramidal upper motor neurons that send their axons down to the spinal
cord via the corticospinal tract, where in humans they synapse directly with anterior horn cells) in motor cortex
§ Mainly UMN signs + marked spastic leg weakness and pseudobulbar palsy
• Pseudobulbar palsy isUMN lesion of muscles of swallowing and talking due to bilateral lesions above the mid-pons
(MS, MND, stroke, central pontine myelinolysis) and is commoner than true bulbar palsy
• Signs: Slow tongue movements, with slow deliberate speech; increased jaw jerk and gag reflexes
• Pseudobulbar affect (PBA) — is mood-incongruent giggling or weeping (“emotional incontinence”)
o Also seen in MS, Wilson’s, and Parkinson’s disease, dementia, nitrous oxide use, and head injury
§ No cognitive decline
• Treatment:
o Due to incurable nature, a multidisciplinary approach is best: neurologist, palliative nurse, hospice, physio, OT, speech therapist,
dietician
o Antiglutamatergic drugs: Riluzole is an Na+-channel blocker inhibiting glutamate release prolongs life by ~3 months; it is costly
§ Caution: LFT (do 3-monthly); contraindicated in hepatic or renal problems.
§ SE: vomiting, increased HR, somnolence, headache, vertigo
o Drooling: Propantheline 15–30mg/8h – in accordance with patient wishes, not well tolerated
o Dysphagia: Blend food; nasogastric tube, or percutaneous catheter gastrostomy
o Respiratory failure (± aspiration pneumonia and sleep apnoea): Non-invasive ventilation (NIV) at home in selected patients
Epilepsy
Epilepsy is a recurrent tendency to spontaneous, intermittent,
abnormal electrical activity in part of the brain, manifesting as
seizures. Many of us would have seizures in abnormal metabolic
circumstances—eg decreased Na+, hypoxia (e.g. reflex anoxic
seizures in faints): yet we would not normally be said to have
epilepsy.
• The prevalence of active epilepsy is ~1%
• Elements of a seizure:
o Prodrome lasting hours or days may rarely precede
the seizure. It is not part of the seizure itself: the patient
or others notice a change in mood or behaviour
o Aura is part of the seizure of which the patient is
aware, and may precede its other manifestations, e.g.
strange feeling in the gut, or an experience such as
déjà vu (disturbing sense of familiarity), or strange
smells or flashing lights. It implies a partial (focal)
seizure, often, but not necessarily, from the temporal lobe
o Seizure:
§ Partial seizures Focal onset, with features referable to a part of
one hemisphere (see BOX). Often seen with underlying structural
disease:
• Simple partial seizure: Awareness is unimpaired, with focal
motor, sensory (olfactory, visual, etc), autonomic or psychic
symptoms. No post-ictal symptoms
• Complex partial seizures: Awareness is impaired. May have
a simple partial onset (=aura). Post-ictal confusion is common
with seizures arising from the temporal lobe, whereas
recovery is rapid after seizures in the frontal lobe
• Partial seizure with secondary generalization: In 2⁄3 of
patients with partial seizures, the electrical disturbance
spreads widely, causing a secondary generalized seizure (usually convulsive)
• Localising features (see image to right above):
o Temporal lobe: Automatisms (complex motor phenomena, but with impaired awareness and no recollection
afterwards e.g. anything from simple lip-smacking/chewing/swallowing right up to singing/kissing/driving car),
dysphasia, Memory phenomena (déjà vu (when everything seems strangely familiar), or jamais vu (everything seems
strangely unfamiliar)), Hippocampal involvement may cause emotional disturbance (including derealisation), Uncal
involvement (hallucinations of smell or taste and a dreamlike state)
o Frontal lobe: Motor features such as posturing, Jacksonian march (a spreading focal motor seizure with retained
awareness, often starting with the face or a thumb), Post-ictal Todd’s palsy
o Parietal lobe: Sensory disturbances — tingling, numbness, pain
o Occipital lobe: Visual phenomena such as spots, lines, flashes.
§ A Primary generalized seizures Simultaneous onset of electrical discharge throughout cortex, with no localizing features
referable to only one hemisphere
• Absence seizures: Brief (≤10s) pauses
• Tonic–clonic seizures: Loss of consciousness. Limbs stiffen (tonic), then jerk (clonic). Post-ictal confusion and drowsiness.
• Myoclonic seizures: Sudden jerk of a limb, face or trunk.
• Atonic (akinetic) seizures: Sudden loss of muscle tone causing a fall, no LOC.
• Infantile spasms/ West syndrome: Commonly associated with tuberous sclerosis.
Michael Grant
lOMoARcPSD|4927727

o Post-ictally there may be headache, confusion, myalgia, and a sore tongue; or temporary weakness after a focal seizure in motor
cortex (Todd’s palsy), or dysphasia following a focal seizure in the temporal lobe
• Causes:
o Idiopathic in 2/3 of patients (often familial)
o Structural: Cortical scarring (eg head injury years before onset), space-occupying lesion, stroke, hippocampal sclerosis (eg after a
febrile convulsion), vascular malformations
o Others: Tuberous sclerosis, sarcoidosis, SLE, PAN
o Non-epileptic causes of seizures: Trauma, stroke, haemorrhage, raised ICP; alcohol or benzodiazepine withdrawal; metabolic
disturbance (hypoxia, Na+, Ca2+, glucose, uraemia); liver disease; infection (eg meningitis, encephalitis, syphilis, cysticercosis, HIV);
High T°; drugs (tricyclics, cocaine, tramadol, theophylline)
• Diagnosis:
o Are these really seizures?
§ Tongue-biting and a slow recovery are very suggestive
§ Not everything that twitches is epilepsy — reflex anoxic convulsions due to
syncope are particularly difficult.
o What type?
§ Onset is the key concern here; If the seizure begins with focal features, it is a
partial seizure, however rapidly it then generalizes
o Any triggers?
§ Alcohol, stress, fevers, certain sounds, flickering lights/TV
§ Triggers are different to provocations, i.e. non-epileptic causes of seizures
o First ever seizure?
§ Is it really the first? Ask about history of faints or funny spells.
§ Was seizure provoked? i.e. no epileptic cause
§ Investigations: admission for 24h for bloods, drugs screen, LP (if safe), EEG,
CT/MRI + enhancement
• An EEG cannot exclude or refute epilepsy; it forms part of the context for
diagnosis. In 1st unprovoked fits, unequivocal epileptiform activity on EEG
helps assess risk of recurrence.
• Treatment:
o Do not advise drugs after one fit, unless risk of recurrence is high (e.g. structural
brain lesion, focal CNS deficit, or unequivocal epileptiform EEG) – if only 1 fit every 2
years, patient may accept risk
o Sudden unexpected death in epilepsy (SUDEP) is more common in uncontrolled
epilepsy, and may be related to nocturnal seizure-associated apnoea or asystole
o Treat with one drug and with one doctor in charge only. Slowly build up doses over 2–
3 months and, if needing to change, titrate one down as the other increases
o Generalized tonic-clonic seizures: Sodium valproate or lamotrigine (often better
tolerated, and less teratogenic)
o Absence seizures: Sodium valproate, lamotrigine or ethosuximide.
o Tonic, atonic and myoclonic seizures: Sodium valproate or lamotrigine; avoid
arbamazepine and oxcarbazepine, which may worsen seizures
o Partial seizures ± secondary generalization: Carbamazepine is 1st-line, then sodium
valproate, lamotrigine
Status Epilepticus
• Consider Status Epilepticus if seizures > 5 min or 2 discrete seizures with no regaining of consciousness inbetween
• Treatment - general measures:
o First stage (0-10 minutes): ABCDE.... and Oxygen
o Second stage (1-60 minutes)
§ Monitoring
§ Emergency AED
§ Intravenous lines
§ Investigation: ?glucose and thiamine, ?treatment of acidosis
o Treatment of convulsive SE
§ Early status (0-10/30mins): lorazepam (IV) 0.07mg/kg (usually a 4mg bolus, repeated once after 20 minutes; rate not
critical)
§ Established status (10/30 – 60/120mins): Phenytoin 20 mg/kg at 50 mg/minute)
§ Refractory status: General anaesthesia with either propofol, midazalom or thiopentone
Multiple sclerosis
Discrete plaques of demyelination occur at multiple CNS sites, from T-cell-mediated immune. Demyelination heals poorly, causing relapsing
and remitting symptoms – but prolonged demyelination causes axonal loss and clinically progressive symptoms
• Prevalence: commoner in temperate areas; average age 30yo; 3:1 f:m
Michael Grant
lOMoARcPSD|4927727

• Early exposure to sunlight/vit. D is important, and vit. D status relates to
prevention of MS and fewer new lesions in established - If
poor diet or low sun exposure, give vit. D to achieve
serum 25(OH)D levels of 50nmol/L
• Symptoms may worsen with heat (eg hot bath) or
exercise (Uhthoff’s phenomenon)
• Presentation:
o Monosymptomatic: unilateral optic neuritis
(pain on eye movement and rapid loss of
central vision); numbness or tingling in the limbs;
leg weakness; brainstem or cerebellar symptoms
(e.g. diplopia, ataxia)
o Progression: Early on, relapses (which can be
stress induced) may be followed by remission and
full recovery. With time, remissions are
incomplete, so disability accumulates.
§ Steady progression of disability from the
outset also occurs, while some patients
experience no progressive disablement at
all
§ Poor prognostic signs: Older female,
motor signs at onset, many MRI lesions
• Diagnosis: This is clinical, as no test is pathognomonic; It requires lesions
disseminated in time and space, unattributable to other causes; thus after a 1st episode further evidence is needed (see McDonald
Criteria)
o ~90% presenting with an MS-like 1st episode and consistent MRI lesions go on to develop MS – MRI may also exclude other causes,
e.g. cord compression
o CSF: Oligoclonal bands of IgG on electrophoresis
o NMO–IgG antibodies are highly specific for Devic’s syndrome (simultaneous inflammation and demyelination of the optic nerve (optic
neuritis) and the spinal cord (myelitis))
• Treament:
o Steroids: Methylprednisolone, eg 1⁄2–1g/24h IV/PO for <3d shortens acute relapses; use sparingly (not more than twice/yr)
o Interferons (IFN-1B & IFN-1A): decrease relapses by 30% in active relapsing-remitting MS; and reduces lesion accumulation on MRI;
SE: flu symptoms, depression, abortion
o Monoclonal antibodies:
§ Alemtuzumab acts against T cells in relapsing-remitting MS
§ Natalizumab acts against VLA-4 receptors that allow immune cells to cross the blood–brain barrier
o Other drugs: Azathioprine may be as good as interferons for relapsing-
remitting MS and is 20≈ cheaper
o Treatments for symptoms:
§ Palliation: Spasticity: Baclofen (GABA receptor agonist, specifically of
the GABAB receptors. Its beneficial effects in spasticity result from
actions at spinal and supraspinal sites)
§ Fatigue: amantadine/modafinal
§ Tremor: Botulinum toxin type A injections improve arm tremor and
functioning
§ Urgency/frequency: If post-micturition residual urine >100mL, teach
intermittent self-catheterization
Myaesthenia gravis is an autoimmune disease mediated by antibodies to nicotinic

acetylcholine receptors (AChR) – with both T and B cells likely to be involved.
• Presentation: Increasing muscular fatigue (Muscle groups affected, in order:
extra- ocular; bulbar (swallowing, chewing); face; neck; limb girdle; trunk
o Look for: ptosis, diplopia, myasthenic snarl on smiling
o Weakness is worsened by: pregnancy, decreased K+, infection , emotion,
exercise, gentamicin, opiates, tetracycline, beta-blockers
o If under 50yr: Commoner in women, associated with other autoimmune
diseases and thymic hyperplasia
o Over 50: it is commoner in men, and associated with thymic atrophy or
thymic tumour, rheumatoid arthritis, and SLE
• Tests:
o Antibodies: Anti-AChR antibodies in 90% (70% in ocular-confined MG); if
seronegative look for MuSK antibodies (muscle specific tyrosine kinase)
o Neurophysiology: Decremental muscle response to repetitive nerve
stimulation ± increased single-fibre jitter.
o Imaging: CT of thymus
o Other: Ptosis improves by >2mm after ice application to the (shut)
affected lid for >2min – cold inhibits action of acetylcholinesterase
• Treatment:
Michael Grant
lOMoARcPSD|4927727

o Symptom control: Anticholinesterase, eg pyridostigmine (60–120mg PO up to 6≈daily; max 1.2g/d)
§ Cholinergic SE: salivation, lacrimation, sweats, vomiting, miosis
o Immunosuppression: Treat relapses with prednisolone. Give osteoporosis prophylaxis.
§ SE: weakness (hence low starting dose). Steroids may be combined with azathioprine
o Thymectomy: Consider if onset before 50yrs old and disease is not easily controlled by anticholinesterases. Expect remission in
25% and worthwhile benefit in a further 50%.
o Myasthenic crisis: Weakness of the respiratory muscles during a relapse can be life-threatening. Monitor forced vital capacity.
Ventilatory support is unlikely to be needed if vital capacity >20mL/kg. Treat with plasmapheresis or IVIG
§ IVIG is an immunomodulating agent that has multiple activities, including; suppression of idiotypic antibodies; saturation of Fc
receptors on macrophages; and suppression of various inflammatory mediators, including cytokines, chemokines, and
metalloproteinases
• Lambert–Eaton myasthenic syndrome (LEMS) can be paraneoplastic (from small-cell lung cancer) or autoimmune. Unlike true MG
there is: Gait difficulty before eye signs; •Autonomic involvement (dry mouth, constipation, impotence); •Hyporeflexia and weakness,
which improve after exercise; Antibody to the pre-synaptic membrane’s voltage-gated Ca2+ channels
o Treatment: 3,4-diaminopyridine or IV immunoglobulin (get specialist help).
o Do regular CXR/high-resolution CT as symptoms may precede the cancer by >4yrs
Headache and Migraine
Headache:
Acute single episode
• With meningism (i.e. neck
stiffness, photophobia,
headache - exclude:
o Meningitis: fever,
photophobia, stiff
neck, purpuric rash,
coma
o Encephalitis: fever,
odd behaviour, fits,
or consciousness ฀
o Subarachnoid
haemorrhage:
sudden-onset, ‘worst
ever’ headache, often
occipital, stiff neck,
focal signs,
consciousness
• Admit immediately for
urgent CT head
o If CT –ve, do LP to
look for signs of
infection or blood
products in the CSF
• Head injury: Headache is common at the site of trauma but may be more generalized. It lasts
~2wks; often resistant to analgesia. Do CT to exclude subdural or extradural haemorrhage
• Venous sinus thrombosis: Subacute or sudden headache, papilloedema
• Sinusitis causes dull, constant ache over frontal or maxillary sinuses, with tenderness ±
postnasal drip. Pain is worse on bending over and seen with coryza
• Low pressure headache: From CSF leak (post LP or skull fracture)
• Acute glaucoma: Typically, elderly, long-sighted people. Constant, aching pain develops
rapidly around one eye, radiating to the forehead
o Symptoms: Markedly reduced vision, visual haloes, nausea/vomiting
o Signs: Red, congested eye
o Attacks may be precipitated by dilating eye-drops, emotional upset or sitting in the dark,
e.g. the cinema
Recurrent acute attacks of headache
• Migraine
• Cluster headache
• Trigeminal neuralgia
• Recurrent (Mollaret’s) meningitis: Suspect if fever/meningism with each headache - send
CSF for herpes simplex PCR
Headaches of subacute onset
• Giant cell arteritis: Exclude in all >50yrs old with a headache that has lasted a few weeks.
Tender, thickened, pulseless temporal arteries; jaw claudication; ESR >40mm/h
Chronic headache
• Tension headache: The usual cause of bilateral, non-pulsatile headache ± scalp muscle
tenderness, but without vomiting or sensitivity to head movement. Stress relief, eg massage or
antidepressants, may be helpful.
Michael Grant
lOMoARcPSD|4927727

• Raised intracranial pressure: Typically worse on waking, lying, bending forward, or coughing. Also vomiting, papilloedema, seizures,
false localizing signs, or odd behaviour. Do imaging to exclude a space-occupying lesion, and consider idiopathic intracranial
hypertension. LP is contraindicated until after imaging.
• Medication overuse (analgesic rebound) headache: Culprits are mixed analgesics (paracetamol + codeine/opiates). Analgesia must be
withdrawn—aspirin or naproxen may mollify the rebound headache
Migraine:
• Symptoms
o Classically: Visual or other aura lasting 15–30min followed within 1h by unilateral,
throbbing headache. Or: Isolated aura with no headache; Episodic severe headaches
without aura, often premenstrual, usually unilateral, with nausea, vomiting ±
photophobia/phonophobia (‘common migraine’). There may be allodynia.
• Signs: None
• Associations: Obesity (weight loss may decrease excess oestrogen/oestradiol production in
adipose tissue—but benefit is unproven); patent foramen ovale
• Prodrome: Precedes headache by hours/days: yawning, cravings, mood/sleep change.
• Aura: Precedes headache by minutes and may persist during it; Visual: chaotic cascading,
distorting, ‘melting’ and jumbling of lines, dots, or zigzags, scotomata or hemianopia;
Somatosensory: paraesthesiae spreading from fingers to face; Motor: dysarthria and ataxia
(basilar migraine), ophthalmoplegia; Speech: (8% of auras) dysphasia or paraphasia, e.g.
phoneme substitution
• Criteria if no aura ≥5 headaches lasting 4–72h + nausea/vomiting (or photo/phonophobia) +
any 2 of: Unilateral, Pulsating, Impairs (or worsened by) routine activity
• Partial triggers Seen in 50%: CHOCOLATE or: chocolate, hangovers, orgasms, cheese, oral
contraceptives, lie-ins, alcohol, tumult, or exercise.
• Differential: Cluster or tension headache, cervical spondylosis, increased BP, intracranial
pathology, sinusitis/otitis media, caries. TIAS may mimic migraine aura.
• Treatment:
o NSAIDs (eg ketoprofen 100mg, dispersible aspirin 900mg/6h) are
good as there is less chance of developing medication misuse
headache (p460), and they have similar efficacy to oral 5HT agonists
(triptans and ergot alkaloids)
o Triptans are generally better tolerated than ergots
§ CI: IHD, coronary spasm, uncontrolled BP, recent lithium, SSRIs,
or ergot use
o Ergotamine 1mg PO as headache starts, repeated at 1⁄2h, up to 3mg in
a day, and 6mg in a week; or better, as a Cafergot® suppository (2mg
ergotamine + 100mg caffeine)
§ Emphasize dangers of ergotamine (gangrene, vascular damage,
pulmonary fibrosis)
§ CI: the Pill; peripheral vascular disease, IHD; pregnancy;
breastfeeding; hemiplegic migraine
• Prevention
o Remove triggers; ensure analgesic rebound headache is not
complicating matters
o Drugs: eg if frequency >2 a month or not responding to drugs acute
treatment drugs:
§ 1st-line: Propranolol 40–120mg/12h, amitriptyline 10–75mg
nocte (SE: drowsiness, dry mouth, vision), topiramate 25–
50mg/12h (SE: memory impairment),or Ca2+ channel blockers
§ 2nd-line: Valproate, pizotifen (effective, but unacceptable weight
gain in some), gabapentin
Michael Grant
lOMoARcPSD|4927727

Guillain-Barré syndrome
Guillain–Barré syndrome (Acute inflammatory
demyelinating polyneuropathy) is a rapid-onset
muscle weakness caused by the immune system
damaging the peripheral nervous system. The
initial symptoms are typically changes in sensation
or pain along with muscle weakness, beginning in
the feet and hands. This often spreads to the arms
and upper body with both sides being involved.
• Signs: A few weeks after an infection
(particularly Campylobacter) a symmetrical
ascending muscle weakness starts.
• Triggers: Campylobacter jejuni, CMV,
mycoplasma, zoster, HIV, EBV, vaccinations.
o The trigger causes antibodies which attack nerves. In 40%, no
cause is found.
• It may advance quickly, affecting all limbs at once, and can lead to
paralysis. There is a progressive phase of up to 4 weeks, followed by
recovery
• Unlike other neuropathies, proximal muscles are more affected, e.g.
trunk, respiratory, and cranial nerves (esp. VII).
• Pain is common (eg back, limb) but sensory signs may be absent.
• Autonomic dysfunction: Sweating, increased pulse, BP changes,
arrhythmias.
• Nerve conduction studies: Slow conduction
• CSF: Protein increase (eg >5.5g/L), normal CSF white cell count
• Respiratory involvement (the big danger) requires transfer to ITU. Do forced vital capacity (FVC) 4 hourly.
o Ventilate sooner rather than later, eg if FVC <1.5L, PaO2 <10kPa, PaCO2 >6kPa
• Rx: IV immunoglobulin 0.4g/kg/24h for 5d.
o Plasma exchange is good too (?more SE).
o Steroids have no role
• Prognosis: Good; ~85% make a complete or near-complete recovery. 10% are unable to walk alone at 1yr.
o Complete paralysis is compatible with complete recovery.
o Mortality: 10%.
Cranial nerve palsies

1. Outline the anatomy of the olfactory nerve and related structures.
2. Define the role of the olfactory epithelium, olfactory bulb, olfactory
tract and piriform cortex
3. Be able to interrogate olfactory function using aromatic bottles or
common scented materials.
The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is
involved in smell. The olfactory cells of the epithelium are bipolar olfactory receptor
neurons which congregate to form the olfactory nerve. The apical poles of these neurons
are covered with non-motile cilia, with the plasma membrane containing odorant-binding
proteins acting as olfactory receptors. The olfactory nerves go through the cribriform
plate and terminate on the dendrites of the mitral cells located in the glomeruli of the
olfactory bulb.
The olfactory bulb (bulbus olfactorius) is a neural structure of the vertebrate forebrain
involved in olfaction, or the sense of smell. As a neural circuit, the olfactory bulb has one
source of sensory input (axons from olfactory receptor neurons of the olfactory
epithelium), and one output (mitral cell axons). It has 4 functions:
• Discriminating among odors
• Enhancing sensitivity of odor detection
• Filtering out many background odors to enhance the transmission of a few select odors
• Permitting higher brain areas involved in arousal and attention to modify the detection or the discrimination of odors
The olfactory tract is a bundle of axons connecting the mitral and tufted cells of the olfactory bulb to several target regions in the brain,
including piriform cortex, amygdala, and entorhinal cortex. The function of the piriform cortex relates to olfaction, which is the perception of
smell. This has been particularly shown in humans for the posterior piriform cortex.
5. Be able to describe the role of ammonia in suspected malingering.

If patient denies ability to smell, then ammonia can be used as a CNV stimulant to detect frunction of smell.
6. List potential causes of olfactory dysfunction

Nearly two-thirds of all chronic anosmia or hyposmia cases are due to prior upper respiratory infections, head trauma, and nasal and
paranasal sinus disease that damage the olfactory neuroepithelium. Additional factors that can influence olfactory function include age
Michael Grant
lOMoARcPSD|4927727

(normal decline), sex (women are generally more sensitive than men), smoking behavior, neurodegenerative diseases, iatrogenic interventions
(e.g., septoplasty, rhinoplasty, turbinectomy, radiation therapy), intranasal neoplasms (e.g., papillomas, hemangiomas, and ameloblastomas),
intracranial tumors or lesions (e.g., Foster Kennedy syndrome, olfactory groove meningiomas, frontal lobe gliomas), epilepsy, psychiatric
disorders, exposure to toxic chemicals, hypothyroidism, renal disease, and kidney disease
7. Define: anosmia and hyposmia

Hyposmia is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected.
7. Describe the anatomy of the optic nerve, optic chiasm, optic tracts, lateral geniculate nuclei and optic radiations.
8. Define the core functions of the optic nerve.
9. Describe the pupillary light reflex.
10. Be able to assess optic nerve function in terms of pupil examination, visual
acuity, assessment of colour vision, bedside assessment of visual fields to
confrontation and examination of the optic fundi (discs in particular).
The optic nerve, also known as cranial nerve II, is a paired nerve that
transmits visual information from the retina to the brain. The optic nerve is
derived from optic stalks during the seventh week of development and is
composed of retinal ganglion cell axons and glial cells.
The optic nerve transmits all visual information including brightness
perception, color perception and contrast (visual acuity). It also conducts
the visual impulses that are responsible for two important neurological
reflexes: the light reflex and the accommodation reflex. The light reflex
refers to the constriction of both pupils that occurs when light is shone into
either eye; the accommodation reflex refers to the swelling of the lens of eye
that occurs when one looks at a near object as in reading (lens adjusts to near vision). Examples of pathology:
• Glaucoma is a group of diseases involving loss of retinal ganglion cells causing optic neuropathy in a pattern of peripheral vision loss,
initially sparing central vision. Glaucoma is associated with increased intraocular pressure that damages the optic nerve as it exits the
eyeball. Although glaucoma does eventually damage the optic nerve, it is primarily a disease of eye not of the nerve.
• Optic neuritis is inflammation of the optic nerve. It is associated with a number of diseases, the most notable one being multiple
sclerosis. The patient will likely experience varying vision loss and eye pain. The condition tends to be episodic.
• Anterior Ischemic Optic Neuropathy is commonly known as "stroke of the optic nerve" and affects the optic nerve head. There is usually
a sudden loss of blood supply and nutrients to the optic nerve head (where the nerve exits the eyeball). Vision loss is typically sudden
and most commonly occurs upon waking up in the morning. This condition is most common in diabetic patients 40–70 years old.
• Optic nerve hypoplasia is the underdevelopment of the optic nerve resulting in little to no vision in the affected eye.
11. Define: anisocoria, miosis, mydriasis and Horner’s syndrome.
Miosis, is a term with various definitions, which generally include constriction of the pupil. The opposite condition, mydriasis, is the dilation of
the pupil. Anisocoria is the condition of one pupil being more dilated than the other.
Horner's syndrome is a combination of symptoms that arises when a group of nerves known as the sympathetic trunk is damaged. The signs
and symptoms occur on the same side as the lesion of the sympathetic trunk. It is
characterized by miosis (a constricted pupil), partial ptosis (a weak, droopy eyelid),
apparent anhidrosis (decreased sweating), with or without enophthalmos
12. Outline the anatomy of the sympathetic innervation of the eye.

13. List common causes of Horner’s syndrome.
Horner syndrome is due to a deficiency of sympathetic activity. The site of lesion to
the sympathetic outflow is on the ipsilateral side of the symptoms. The following are
examples of conditions that cause the clinical appearance of Horner's syndrome:
• First-order neuron disorder: Central lesions that involve the hypothalamospinal
tract (e.g. transection of the cervical spinal cord).
• Second-order neuron disorder: Preganglionic lesions (e.g. compression of the
sympathetic chain by a lung tumor) that releases acetylcholine (e.g. pancoast).
• Third-order neuron disorder: Postganglionic lesions at the level of the internal
carotid artery (e.g. a tumor in the cavernous sinus or a carotid artery dissection)
that releases norepinephrine.
• Partial Horner's syndrome: In case of a third-neuron disorder, anhidrosis is limited
to the middle part of the forehead or can be absent, resulting in a partial Horner's
syndrome
Causes can be divided according to the presence and location of anhidrosis:
• Central (anhidrosis of face, arm and trunk)
Syringomyelia
Multiple sclerosis
Encephalitis
Brain tumors
Michael Grant
lOMoARcPSD|4927727

Lateral medullary syndrome
• Preganglionic (anhidrosis of face)
Cervical rib traction on stellate ganglion
Thyroid carcinoma
Thyroidectomy
Goiter
Bronchogenic carcinoma of the superior fissure (Pancoast
tumor) on apex of lung
Klumpke paralysis
Trauma - base of neck, usually blunt trauma, sometimes
surgery.
As a complication of tube thoracostomy
Thoracic aortic aneurysm
• Postganglionic (no anhidrosis)
Cluster headache - combination termed Horton's headache
An episode of Horner's syndrome may occur during a migraine attack and be relieved afterwards[2]
Carotid artery dissection/carotid artery aneurysm
Cavernous sinus thrombosis
Middle ear infection
15. Define red desaturation and its clinical significance

Color desaturation refers to a qualitative inter-eye difference in color perception that can be tested by comparing vision of a red object with
each eye. A patient with monocular "red desaturation" may report that the red color appears "washed out," pink, or orange when viewed with
the affected eye – associated w/ Optic neuritis
16. List the causes of optic disc swelling.

The most common causes of optic nerve swelling are non-arteritic anterior ischaemic optic neuropathy (35%), optic neuritis (31%) and
intracranial pathology (14%).
• Unilateral optic disc swelling is more likely to be due to demyelinating optic neuritis, non-arteritic anterior ischaemic optic neuropathy,
retinal vein occlusion and diabetic papillopathy.
• Bilateral swelling is more likely to be due to papilloedema, toxic optic neuropathy and malignant hypertension
Cocaine drop test: Cocaine eyedrops block the reuptake of post-ganglionic norepinephrine resulting in the dilation of a normal pupil
from retention of norepinephrine in the synapse. However, in Horner's syndrome the lack of norepinephrine in the synaptic cleft causes
mydriatic failure – hence no dilation on cocaine application.
• A more recently introduced approach that is more dependable and obviates the difficulties in obtaining cocaine is to apply the alpha-
agonist apraclonidine to both eyes and observe the increased mydriatic effect (due to hypersensitivity) on the affected side of Horner
syndrome (the opposite effect to what the cocaine test would produce in the presence of Horner's).
Intracranial conditions
• Causes of raised ICP:
o Tumour.
o Cerebral trauma.
o Intracerebral or subdural haemorrhage.
o Cerebral inflammation/infection.
o Cerebral abscess.
o Idiopathic intracranial hypertension (pseudotumor cerebri), a condition with elevated CSF pressure and no mass lesion.
o Respiratory failure.
o Chiari malformation.
o Acute mountain sickness and high-altitude cerebral oedema.
o Lyme disease.
o Some medications have been associated with raised ICP - eg,
tetracycline, minocycline, lithium, isotretinoin, nalidixic acid and
corticosteroids (both use and withdrawal).
Optic nerve conditions
• Optic neuritis.
• Optic neuropathy:
• Arteritic ischaemic optic neuropathy (giant cell arteritis).
• Non-arteritic anterior ischaemic optic neuropathy.
• Toxic optic neuropathy (eg, methanol poisoning).
• Compressive optic neuropathy (eg, thyroid eye disease).
• NB: congenitally anomalous optic discs may appear swollen.
Michael Grant
lOMoARcPSD|4927727

• Infiltration of the disc by sarcoid, glioma, lymphoma.
Vascular causes
• Retinal vein occlusion.
• Retinal artery occlusion.
• Malignant hypertension.
• Acute lymphocytic leukaemia (through infiltration of retinal vessels by immature
lymphocytes).
Conditions affecting the globe
• Glaucoma: central vein occlusion.
• Long periods of weightlessness.
• Pan or posterior uveitis.
• Posterior scleritis.
• Irvine-Gass syndrome (see separate Macular Oedema article).
• Infiltration or inflammation (eg, sarcoid, leukaemia).
• Carbon dioxide retention.
• Parahypothyroidism.
• Uraemia.
17. Define papilloedema, papillitis and optic atrophy.

Papilledema (or papilloedema) is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can
occur over a period of hours to weeks.
• Pseudopapilledema is a normal variant of the optic disk, in which the disk appears elevated, with indistinct margins and a normal vascular
pattern. Pseudopapilledema sometimes occurs in hyperopic individuals
• The pink rim of disc contains nerve fibers; a normal ratio is 0.3-0.5
Optic papillitis is a specific type of optic neuritis. Inflammation of the optic nerve head is called "papillitis" or "intraocular optic neuritis";
inflammation of the orbital portion of the nerve is called "retrobulbar optic neuritis" or "orbital optic neuritis". It is often associated with
substantial losses in visual fields, pain on moving the globe, and sensitivity to light pressure on the globe. It is often an early sign of
multiple sclerosis.
• Papillitis may have the same appearance as papilledema but may be unilateral, whereas papilledema is almost always bilateral.
• Papillitis can be differentiated from papilledema by an afferent pupillary defect (Marcus Gunn pupil – swinging light test), by its greater
effect in decreasing visual acuity and color vision, and by the presence of a central scotoma.
• Increased intracranial pressure can cause both papilledema and a sixth (abducens) nerve palsy, papilledema can be differentiated from
papillitis if esotropia (inward strabismus) and loss of abduction are also present.
Optic atrophy refers to the death of the retinal ganglion cell axons that comprise the optic nerve with the resulting picture of a pale optic
nerve on funduscopy. Optic atrophy is an end stage that arises from myriad causes of optic nerve damage anywhere along the path from the
retina to the lateral geniculate. Because the optic nerve fiber layer is thinned or absent the disc margins appear sharp and the disc is pale,
probably reflecting absence of small vessels in the disc head.
The causes for optic atrophy include:
• Compressive – secondary to papilledema, tumor, bony growth (fibrous dysplasia,
osteopetrosis), thyroid eye disease, chiasmal (pituitary etc), optic nerve sheath
meningioma, disc drusen, increa sed intraocular pressure (glaucoma)
• Vascular – arteritic and non-arteritic ischemic optic neuropathy, diabetes,
• Inflammatory – sarcoid, systemic lupus, Behcet’s, demyelination (MS), etc.
• Infectious – viral, bacterial, fungal infections - herpes, TB, bartonella, etc.
• Toxic & nutritional – many medications such as ethambutol, amiodarone, methanol,
vitamin deficiency etc.
• Metabolic – diabetes
• Neoplastic – lymphoma, leukemia, tumor, glioma
• Genetic – Autosomal dominant optic atrophy (OPA1), Leber’s hereditary optic atrophy,
Leber's hereditary optic neuropathy, as a late complication of retinal degneration.
• Radiation optic neuropathy
• Traumatic optic neuropathy
18. Outline the stages of papilloedema.

Stage 0 - Normal Optic Disc Blurring of nasal, superior and inferior poles in
inverse proportion to disc diameter. Radial nerve fiber layer (NFL) without NFL
tortuosity.
Rare obscuration of a major blood vessel, usually on the upper pole.
Stage 1 -Very Early Papilledema Obscuration of the nasal border of the disc. No
elevation of the disc borders. Disruption of the normal radial NFL arrangement with
grayish opacity accentuating nerve fiber layer bundles. Normal temporal disc
margin. Subtle grayish halo with temporal gap (best seen with indirect
ophthalmoscopy).
Concentric or radial retrochoroidal folds.
Stage 2 - Early Papilledema Obscuration of all borders. Elevation of the nasal
border. Complete peripapillary halo.
Michael Grant
lOMoARcPSD|4927727

Stage 3 - Moderate Papilledema Obscurations of all borders. Increased diameter of optic nerve head. Obscuration of one or more segments
of major blood vessels
leaving the disc. Peripapillary halo-irregular outer fringe with finger-like extensions.
Stage 4 - Marked Papilledema Elevation of the entire nerve head. Obscuration of all borders. Peripapillary halo. Total obscuration on the disc
of a segment of a major
blood vessel.
Stage 5 - Severe Papilledema Dome-shaped protrusions representing anterior expansion of the optic nerve head. Peripapillary halo is narrow
and smoothly demarcated.
24. Describe the core features of an oculomotor (IIIn) palsy in terms of

eye position, lid position, pupil involvement and pain.
Third nerve palsy is an eye condition resulting from damage to the third cranial nerve
or a branch thereof. As the name suggests, the oculomotor nerve supplies the majority
of the muscles controlling eye movements. Thus, damage to this nerve will result in the
affected individual being unable to move his or her eye normally. In addition, the
nerve also supplies the upper eyelid muscle (levator palpebrae superioris) and the
muscles responsible for pupil constriction (sphincter pupillae).
25. Define the ‘laws of projection’ and their role in the assessment of
diplopia.
Law of Projection of Images: This law establishes that an object that forms its image
on any point in the retina is projected to a point in visual space directly opposite, and when a distant object is viewed with two normally seeing
eyes, the visual axes are parallel. Conjugate gaze up and to the right, for example, is accomplished by conjugate movement of the eyes to the
right and simultaneous and equal innervation to the right SR and the left IO muscles. Each EOM moves the eye in the same distance and at
the same speed to attain precise "foveation." If there is an interocular difference in the speed or extent of eye movement, the fixational target
falls on non-corresponding points in the retina and diplopia results. It follows that conjugate movement of the eyes further into the field of the
weakened eye muscle will increase the amount of retinal non-correspondence and, therefore, increase the distance between disparate images.
• 1) Is your double vision present in straight-ahead gaze?
• 2) Do the images separate more when you look to your right or left?
• 3) If it worsens in right gaze, does it worsen in gaze right and up or gaze right and down?
• 4) What happens if you tilt your head to the right or left shoulder?
26. Outline the significance of a painful IIIn palsy and its relationship to aneurysmal disease.
Painful third nerve palsies are a sign of posterior communicating artery aneurysm
27. List common causes of a III nerve palsy.

Congenital oculomotor palsy
• The origins of the vast majority of congenital oculomotor palsies are unknown, or idiopathic to use the medical term. There is some
evidence of a familial tendency to the condition, particularly to a partial palsy involving the superior division of the nerve with an autosomal
recessive inheritance. The condition can also result from aplasia or hypoplasia of one or more of the muscles supplied by the oculomotor
nerve. It can also occur as a consequence of severe birth trauma.
Acquired oculomotor palsy

• Vascular disorders such as diabetes, heart disease, atherosclerosis and aneurysm, particularly of the posterior communicating artery
• Space occupying lesions or tumours, both malignant and non-malignant
• Inflammation and infection
• Trauma
• Demyelinating disease (multiple sclerosis)
• Autoimmune disorders such as myasthenia gravis
• Post-operatively as a complication of neurosurgery
• Cavernous sinus thrombosis
28. Describe the core features of a trochlear (IV nerve) palsy in terms of symptoms, eye
position, head position and Bielschowsky phenomenon.
Fourth cranial nerve palsy also known as Trochlear nerve palsy, is a condition affecting
Cranial Nerve 4 (IV), the Trochlear Nerve, which is one of the Cranial Nerves that causes
weakness or paralysis to the Superior Oblique muscle superior oblique muscle that it
innervates. This condition often causes vertical or near vertical double vision as the
weakened muscle prevents the eyes from moving in the same direction together.
• Sup. Oblique usually pulls globe down and out
• Head tilts to unaffected side to compensate
• Bielschowsky's head tilt test:
§ Step 1: Determine which eye is hypertropic in primary position. If there is right hypertropia in primary position, then the
depressors of the R eye (IR/SO) or the elevators of the L eye are weak (SR/IO).
Michael Grant
lOMoARcPSD|4927727

§ Step 2: Determine whether the hypertropia increases on right or left
gaze. The vertical rectus muscles have their greatest vertical action
when the eye is abducted. The oblique muscles have their greatest
vertical action when the eye is adducted.
§ Step 3: Determine whether the hypertropia increases on right or left
head tilt. During right head tilt, the right eye intorts (SO/SR) and the
left eye extorts (IO/IR).
o When a healthy individual tilts their head, the superior oblique and
superior rectus muscles of the eye closest to the shoulder keep
the eye level. The inferior oblique and inferior rectus muscles
keep the other eye level. In patients with superior oblique palsy,
the superior rectus muscle’s action is not counteracted by the
superior oblique muscles. This leads to vertical deviation of the
affected eye when the head is tilted towards the effected eye.
However, there is no deviation when the head is tilted towards
the unaffected eye because the superior oblique muscle is not
stimulated in the effected eye, but rather it is stimulated in the
unaffected eye. When there is a discrepancy in ocular deviation
based on which way the head is tilted, the patient is diagnosed with
unilateral palsy of the superior oblique muscle due to damage in the
Trochlear Nerve.
Because the fourth cranial nerve is the thinnest and has the longest
intracranial course of the cranial nerves, it is particularly vulnerable to
traumatic injury.
29. List common causes of a IV nerve palsy

As with all CN palsies:
• Tumour
• Thrombosis/Vascular origin (assess risk: atherosclerotic, diabetes, heart disease)
• Trauma
• MS
• Infection
32. Define: ‘false localizing sign’.

Sixth nerve palsies are infamous as “false localizing signs.” Neurological signs are
described as “false localizing” if they reflect dysfunction distant or remote from the
expected anatomical location of pathology. Isolated sixth nerve palsies in children are
assumed to be due to brain tumors until proven otherwise.
Sixth nerve palsies are the most common false-localizing sign of raised ICP. In one
series of 101 cases of IIH, 14 cases were noted, 11 unilateral and three bilateral.17
Stretching of the nerve in its long intracranial course or compression against the petrous
ligament or ridge of the petrous temporal bone have been suggested as the mechanism
for false-localizing sixth nerve palsy.
33. Describe the features of an INO and localize the lesion.

Internuclear ophthalmoplegia (INO) is a disorder of conjugate lateral gaze in which the
affected eye shows impairment of adduction. When an attempt is made to gaze
contralaterally (relative to the affected eye), the affected eye adducts minimally, if at
all. The contralateral eye abducts, however with nystagmus. Additionally, the divergence
of the eyes leads to horizontal diplopia. That is, if the right eye is affected the patient will
"see double" when looking to the left, seeing two images side-by-side. Convergence is
generally preserved.
34. Describe the anatomy of the Trigeminal (V) cranial nerve in terms of nuclei
(sensory and motor), intracranial course and innervation of facial sensation
(V1-V3) and motor innervation of the muscles of mastication.
35. Describe the corneal reflex and its significance (afferent and
efferent limbs).
The corneal reflex, also known as the blink reflex, is an involuntary
blinking of the eyelids elicited by stimulation of the cornea (such as
by touching or by a foreign body), though could result from any
peripheral stimulus.
The reflex is mediated by:
• the nasociliary branch of the ophthalmic branch (V1) of the 5th
cranial nerve (trigeminal nerve) sensing the stimulus on the cornea,
lid, or conjunctiva (i.e., it is the afferent).
Michael Grant
lOMoARcPSD|4927727

• the temporal and zygomatic branches of the 7th cranial nerve (Facial nerve) initiating the motor response (i.e., it is the efferent).
• the centre (nucleus) in the pons of brain stem.
36. Describe the significance of the jaw jerk.

The jaw jerk reflex or the masseter reflex is a stretch reflex used to test the status of a patient's trigeminal nerve (CN V). It is usually absent or
very slight but it can help distinguish an upper cervical cord compression. Lesions that are above the foramen magnum may cause a
hyperactive jaw jerk.
38. Describe potential causes of Trigeminal nerve dysfunction.

In trigeminal neuralgia, also called tic douloureux, the trigeminal nerve's function is disrupted. Usually, the problem is contact between a
normal blood vessel — in this case, an artery or a vein — and the trigeminal nerve at the base of your brain. This contact puts pressure on the
nerve and causes it to malfunction.
Trigeminal neuralgia can occur as a result of aging, or it can be related to multiple sclerosis or a similar disorder that damages the myelin
sheath protecting certain nerves. Less commonly, trigeminal neuralgia can be
caused by a tumor compressing the trigeminal nerve.
Some people may experience trigeminal neuralgia due to a brain lesion or
other abnormalities. In other cases, surgical injuries, stroke or facial trauma
may be responsible for trigeminal neuralgia.
Triggers:
• Shaving
• Touching your face
• Eating
• Brushing your teeth
• Putting on makeup
• Encountering a breeze
• Washing your face
41. Describe the significance of bilateral cortical innervation.

42. Describe the core clinical features of an upper motor neurone and
lower motor neurone facial nerve palsy and their potential aetiologies.
Branches of the facial nerve leaving the facial motor nucleus (FMN) for the
muscles do so via both left and right posterior (dorsal) and anterior (ventral) routes. The posterior components receive motor input from both
hemispheres of the cerebral cortex (bilaterally), whereas the anterior components receive strictly contralateral input. This means that the
temporal branch of the facial nerve receives motor input from both hemispheres whereas the rest do not.
An UMN lesion occurring in the left hemisphere would eliminate motor input to the right anterior
FMN component, thereby paralyzing the right mid- and lower-face. The posterior component,
however, although now only receiving input from the right hemisphere, is still able to allow the
temporal branch to sufficiently innervate the entire forehead.
However, the case if different from LMN lesion due to close physical proximity of branches and the
fact that the contralateral innervation has already decussated. A lesion on the left side would
inhibit muscle innervation from both the left posterior and anterior routes, thus paralyzing the
whole left side of the face (Bell’s palsy).
45. Describe the anatomy of the vestibulocochlear (VIII) nerve in terms

of nuclei, distinct auditory and vestibular functions.
46. Describe the symptoms of VIII nerve dysfunction.
Damage to the vestibulocochlear nerve may cause the following symptoms:
• Hearing loss
• Vertigo
• False sense of motion
• Loss of equilibrium (in dark places)
• Nystagmus
• Motion sickness
• Gaze-evoked tinnitus
47. Define: vertigo.

Is this vertigo? Definition: An illusion of movement, often rotatory, of the patient or his surroundings. In practice, simple ‘spinning’ is rare—the
floor may tilt, sink, or rise, or “I veer sideways on walking as if pulled by a magnet”. Vertigo is always worsened by movement.
• Associated symptoms: Difficulty walking or standing (may even fall suddenly to the ground), relief on lying or sitting still; nausea,
vomiting, pallor, sweating. Associated hearing loss or tinnitus implies labyrinth or VIIIth nerve involvement.
• What is not vertigo: Faintness may be due to anxiety with associated palpitations, tremor, and sweating. Light-headedness may be
due to anaemia, orthostatic hypotension, or effort in an emphysematous patient. But in all of these there is no illusion of movement or
typical associated symptoms. Lost awareness during attacks should prompt thoughts of epilepsy or syncope, not vertigo.
48. Describe the clinical features distinguishing peripheral and central
Michael Grant
lOMoARcPSD|4927727

nystagmus.
Central causes of nystagmus are often pendular, do not have a fast-slow
phase, and is vertical in direction; even though horizontal and jerk
nystagmus can occur with central lesions. Peripheral origin of nystagmus
typically present as a horizontal and jerk nystagmus. In a peripheral lesion,
jerk nystagmus has its fast phase beating away from the side of lesion while
central lesion has its fast phase beating towards the side of lesion. A better
way to do so is by fixing the gaze and see if nystagmus is reduced or
relieved. In peripheral nystagmus, it is often relieved by gaze-fixation while
central nystagmus is not. Another important differentiating clue is the
associative sign and symptoms; including cerebellar sign such as ataxia,
dysdiadokinesia, intention tremor, and scanning speech (ataxic dysarthria
in which spoken words are broken up into separate syllables); and brainstem
sign such as bulbar palsy, hemiplegia, or unilateral sensory loss. But this
may not be enough, central lesion can be cerebellar, brainstem, posterior
hemisphere and cerebral hemisphere.
The most common causes of the inner ear trouble that leads to peripheral
vertigo are:
• Benign paroxysmal positional vertigo (BPPV)
• Vestibular neuronitis
• Meniere's disease (disorder of the inner ear that is characterized by episodes of feeling like the world is spinning (vertigo), ringing in
the ears (tinnitus), hearing loss, and a fullness in the ear)
• Labyrinthitis (viral infection)
• Perilymph fistula (trauma or sudden pressure change)
• Superior semicircular canal dehiscence syndrome (SSCDS) - caused by a thinning or complete absence of the part of the temporal
bone overlying the superior semicircular canal of the vestibular system (usually congenital but can be trigger by trauma)
Central vertigo is caused by a disease or injury to the brain, such as:
• Head injuries
• Illness or infection
• Multiple sclerosis
• Migraines
• Brain tumors
• Strokes
• Transient ischemic attacks
51. Describe the contents of the jugular foramen and the syndrome
associated with lesions in this area.
Cranial nerves IX, X, and XI and the internal jugular vein pass through the jugular
foramen.
The jugular foramen may be subdivided into three compartments, each with their own
contents.
• The anterior compartment transmits the inferior petrosal sinus and glossopharyngeal
nerve (CN IX)
• The intermediate transmits the vagus and accessory nerves (aka cranial nerves number
X, and XI respectively).
• The posterior transmits the sigmoid sinus (becoming the internal jugular vein) and some
meningeal branches from the occipital and ascending pharyngeal arteries.
Jugular foramen syndrome, or Vernet's syndrome is characterized by the paresis of 9th–
11th (with or without 12th) cranial nerves together.
Symptoms of this syndrome are consequences of this paresis. As such, in an affected patient,
you may find:
• Dysphonia/hoarseness
• Soft palate dropping
• Deviation of the uvula towards the normal side
• Dysphagia
• Loss of sensory function from the posterior 1/3 of the tongue
• Decrease in the parotid gland secretion
• Loss of gag reflex
Michael Grant
lOMoARcPSD|4927727

• Sternocleidomastoid and trapezius muscles paresis
Causes:
• Meningiomas
• Schwannomas (Acoustic neuroma)
• Trauma
• Infections
• Cholesteatoma (very rare)
• Obstruction of the jugular foramen due to bone diseases
54. Describe the core features of a bulbar palsy and pseudobulbar palsy.
To summarize briefly, the most important and common syndrome caused
by a disorder of the glossopharyngeal nerve (craniel nerve IX) is
glossopharyngeal neuralgia. Also, swallowing function occasionally is
compromised in a rare but disabling form of tardive dyskinesia called
tardive dystonia, because the upper motor portion of the glossopharyngel
nerve projects to the basal ganglia and can be affected by lesions in the
basal ganglia. Vagus nerve function (craniel nerve X) can be compromised
in schizophrenia, bulimia, obesity, and major depression. A cervical
lesion to the nerve roots of the spinal accessory nerve (craniel nerve XI) can
cause a cervical dystonia, which sometimes is misdiagnosed as a
dyskinesia related to neuroleptic use. Finally, unilateral hypoglossal
(craniel nerve XII) nerve palsy is one of the most common
mononeuropathies caused by brain metastases. Supranuclear lesions of
cranial nerve XII are involved in pseudobulbar palsy and ALS, and lower
motor neuron lesions of cranial nerve XII can also be present in bulbar
palsy and in ALS patients who also have lower motor neuron involvement.
Bulbar palsy:
Bulbar relates to the medulla. Bulbar palsy is the result of diseases
affecting the lower cranial nerves (VII-XII). A speech deficit occurs due to
paralysis or weakness of the muscles of articulation which are supplied by
these cranial nerves. The causes of this are broadly divided into:
• ALS
• Motor neurone disease
• Syringobulbia
• Guillain-Barre syndrome
• Poliomyelitis
• Subacute menignitis (carcinoma, lymphoma)
• Neurosyphilis
• Brainstem CVA
The clinical features include:
• Gag reflex – absent
• Tongue – wasted, fasciculations - “wasted, wrinkled, thrown into folds (decreased tone) and increasingly motionless”.
• Palatal movement (swallowing reflex induced by stimulation of the palate) – absent.
• Jaw jerk – absent or normal
• Speech – nasal - “indistinct (flaccid dysarthria), lacks modulation and has a nasal twang”
• Emotions – normal
• Other – signs of the underlying cause, e.g. limb fasciculations.
Pseudobulbar palsy
Pseudobulbar palsy results from disease of the corticobulbar tracts. Bilateral tract damage must occur for clinically evident disease as the
muscles are bilaterally innervated.
• Bilateral CVAs affecting the internal capsule.
• ALS
• Multiple sclerosis
• Motor neurone disease
• High brainstem tumours
• Head injury
The clinical features include:
• Gag reflex – increased or normal
• Tongue – spastic “it cannot be protruded, lies on the floor of the mouth and is small and tight (increased tone)”.
• Palatal movement – absent.
• Jaw jerk – increased
• Speech – spastic: “a monotonous, slurred, high-pitched, ‘Donald Duck’ dysarthria” that “sounds as if the patient is trying to squeeze out
words from tight lips”.
• Emotions – labile; incongruent with moods (crying when happy, giggling when sad)
• Other – bilateral upper motor neuron (long tract) limb signs
57. Define: dysarthria, dysphonia and dysphasia
Michael Grant
lOMoARcPSD|4927727

Dysarthria, encompasses a group of motor speech disorders caused by a disturbance in the
neuromuscular control of speech. Resulting from neurological injury of the motor component of
the motor-speech system and is characterized by poor articulation of phonemes.
Dysphonia is classified as either an organic or a functional disorder of the larynx. Dysphonia,

commonly referred to as hoarse voice, refers to dysfunction in the ability to produce voice. For
voice to be classified as "dysphonic", abnormalities must be present in one or more vocal
parameters: pitch, loudness, quality, or variability.
Dys/Aphasia is an inability to comprehend and formulate language because of damage to

specific brain regions (areas of the brain responsible for language comprehension and
expression). This damage is typically caused by a cerebral vascular accident, or head trauma,
however these are not the only possible causes.
59. Describe the anatomy and function of the accessory (XI) nerve and its clinical assessment.
60. Describe potential causes of accessory nerve dysfunction.
The accessory nerve is a cranial nerve that controls the sternocleidomastoid and trapezius muscles. As part of it was formerly believed to
originate in the brain, it is considered the eleventh of twelve cranial nerves, or simply cranial nerve XI. Traditional descriptions of the accessory
nerve divide it into two parts: a spinal part and a cranial part. However, because the cranial component rapidly joins the vagus nerve,
becoming an integral part of said nerve, modern descriptions often consider the cranial component to be part of the vagus nerve and not
part of the accessory nerve proper. For this reason, in contemporary discussions of the accessory nerve, the common practice is to dismiss the
cranial part altogether, referring to the accessory nerve specifically as the spinal accessory nerve.
The accessory nerve is tested by evaluating the function of the trapezius and sternocleidomastoid muscles.
• The trapezius muscle is tested by asking the patient to shrug their shoulders with and without resistance. The sternocleidomastoid muscle
is tested by asking the patient to turn their head to the left or right against resistance.
• One-sided weakness of the trapezius may indicate injury to the nerve on the same side of an injury to the spinal accessory nerve on
the same side
• Weakness in head-turning suggests injury to the contralateral spinal accessory nerve: a weak leftward turn is indicative of a weak
right sternocleidomastoid muscle (and thus right spinal accessory nerve injury)
Renal
Quick renal physiology:
• The kidneys receive 25% of cardiac output
• Blood pressure is progressively reduced from the renal artery to the glomerular
capillaries. Glomerular capillary pressure provides the hydraulic force for filtration across
the glomerular basement membrane
• Renin increases blood pressure via the renin-angiotensin-aldosterone system and is
secreted by the juxtaglomerular cells, in response to three stimuli:
o Carotid baroreceptor detection of low pressure
o The juxtaglomerular apparatus is a specialized structure formed by the distal
convoluted tubule and the glomerular afferent arteriole made of cells derived from
smooth muscle cells; located near the vascular pole of the glomerulus and its main
function is to regulate blood pressure of the afferent arteriole secrete renin
when blood pressure in the arteriole falls
o The macula densa is a collection of specialized epithelial cells in the distal
convoluted tubule that detect sodium concentration of the fluid in the tubule.
In response to elevated sodium, the macula densa cells trigger contraction of
the afferent arteriole, reducing flow of blood to the glomerulus and the
glomerular filtration rate.
• Functions of the Kidney:
o EXCRETION
§ Sodium, Potassium, Hydrogen, Water
o REGULATION
§ Blood pressure control, Acid-base balance, Electrolyte balance
• pH control by H+ secretion and HCO3 generation (via glutamine)
• Conditions associated with sodium and water loss:
o Losses from the gut
§ Vomiting and diarrhoea
o Loss from the kidney
§ Osmotic diuresis - e.g. glucose in poorly controlled diabetes
mellitus
§ Diuresis secondary to drugs
Michael Grant
lOMoARcPSD|4927727

o Loss from skin
§ Dehydration
§ Burns
• Conditions associated with sodium and water retention:
o Pregnancy
o Heart failure
o Liver failure
o Kidney failure
o SYNTHESIS
§ Erythropoietin, Activated vitamin D
• Symptoms of abnormal kidney function often occur very late when kidney function is
poor (< 20-30% kidney function):
o Fatigue and Pallor (anaemia 2o to Epo deficiency)
o Breathlessness (fluid retention +/- acidosis)
o Leg swelling and hypertension (Oedema = fluid retention)
o Nausea, anorexia, weight loss (retained toxins)
o Itch (retained toxins)
o Bone pain (vitamin D defect)
o Lower Urinary Tract Symptoms:
§ Dysuria: pain and stinging when urine is passed
§ Urgency: excessive urge to urinate
§ Frequency: desire to pass urine at frequent intervals, even if the bladder is not
full of urine
§ Abnormal stream: weak, dribbling
§ Haematuria: visible or microscopic
§ Protein- or albuminuria: glomerular pathology
§ Nocturia: need to urinate, particularly at night
• Hypertension and the kidney:
o Hypertension and the rule of halves:
§ Hypertension is common affecting up to 25% of a general population
§ Half of those who are hypertensive have been identified
§ Half of those identified are on treatment
§ Half of those treated have their blood pressure well
controlled
o Causes:
§ Essential hypertension - the majority (85%)
§ Secondary hypertension - the minority – chronic renal
disease
• Renal vascular disease
• Endocrine disorders
• Co-arctation of the aorta
• Drugs e.g. NSAIDs
• Alcohol
UTI is the presence of a pure growth of >105 organisms per mL of fresh

MSU
• Lower UTI: urethra (urethritis), bladder (cystitis), prostate (prostatitis).
• Upper UTI: renal pelvis (pyelonephritis)
• Can be simple or complicated. Considered complicated if:
o Strange person (male, child, immunocompromised)
o Strange function (incomplete voiding, retention, obstruction),
o Strange anatomy (congenital malformation, post-surgery)
o Strange organism
• Risk factors: female gender, sexual intercourse, spermicide, pregnancy,
menopause, immunocompromise (immunosuppression, DM); urinary tract
(obstruction, stones, catheter, malformation)
o Urine in catheterized bladders is almost always infected; don’t
investigate unless the patient is ill
• Symptoms:
o Acute pyelonephritis: High fever, rigors, vomiting, loin pain and
tenderness, oliguria (if acute kidney injury).
o Cystitis: Frequency, dysuria, urgency, haematuria, suprapubic pain
o Prostatitis: Flu-like symptoms, low backache, few urinary symptoms,
tender prostate on PR
• Tests:
o If symptoms are present, dipstick the urine; treat empirically if nitrites
or leucocytes are +ve
o If dipstick is –ve but patient symptomatic, send an MSU for lab MC&S
o Causes of sterile pyuria (pus in urine):
Michael Grant
lOMoARcPSD|4927727

o TB
o Treated UTI <2 weeks prior
o Appendicitis
o Papillary necrosis (e.g. DM or Analgesic excess)
o USS
o Computed tomography of Kidneys, Ureters, Bladder (CTKUB)
• Preventions:
o Drink more water
o Cranberry juice may reduce bacterial adhesion
o If very recurrent, consider ABx prophylaxis Computed tomography of
Kidneys, Ureters, Bladder
Acute kidney injury = a decrease in GFR which occurs within hours to weeks
and is potentially reversible
Acute Kidney Injury (AKI)

• AKI affects up to 25% of hospitalised patients
• AKI prolongs hospital stay
• AKI associated with premature mortality
• AKI linked to rapid progression of chronic kidney disease
Normal kidney function depends on

• Perfusion with adequate pressure and oxygen
• Intact nephrons (glomeruli and tubules)
• Free urinary drainage
• Use following criteria for diagnosing AKI:

o Rise in creatinine >26μmol/L in 48hrs
o Rise in creatinine >1.5 ≈ baseline (best figure in last 3/12)
o Urine output <0.5mL/kg/h for >6 consecutive hours
Acute kidney injury causes:

• Pre-renal: disordered perfusion of a kidney which is structurally
normal
o True Volume Depletion: haemorrhage, GI tract losses
o Hypotension – septic shock, cardiogenic shock (“pump failure”)
§ Apparently “normal” BP may be inadequate for continued
renal perfusion in some patients
o Oedematous States – advanced cardiac failure, advanced liver
failure
o Renal artery stenosis ± ACE-i
• Renal: damage to the nephrons (glomeruli +/- tubules), sometimes
after prolonged pre-renal insults
o Tubular — acute tubular necrosis (ATN - result of pre-renal damage or nephrotoxins such as drugs
(eg aminoglycosides - monitor trough level [drug level at time due for next dose], rather than peak
[1hr after dose]), radiological contrast, and myoglobinuria in rhabdomyolysis), myeloma,
Increased Ca2+
o Glomerular — SLE, HSP (systemic IgA nephropathy), drugs, infections, glomerulonephritides
o Interstitial — drugs, infiltration with, eg lymphoma, infection, tumour lysis syndrome following
chemotherapy (Hyperkalaemia, hyperphosphataemia, hypocalcaemia [because of phosphate],
Hyperuricemia, lactic acidosis)
o Vascular — vasculitis, malignant BP, thrombus or cholesterol
emboli from angiography, HUS/TTP, large vessel occlusion, eg
dissection
• Post-renal: urinary drainage obstructed
o Luminal — stones, clots, sloughed papillae
o Mural — malignancy (eg ureteric, bladder, prostate), BPH, strictures
o Extrinsic compression — malignancy (esp pelvic), retroperitoneal fibrosis
§ Absolutely NO urine? Exclude obstruction first:
Is the bladder palpable?
If catheter in situ: – Flush and consider changing
§ If no catheter: Pass one!
§ Obstruction may still be present above the level of the bladder outlet – an urgent USS is needed
§ If signs of obstruction and hydronephrosis on CT/ USS then discuss with urology regarding cystoscopy and retrograde stents
or nephrostomy insertion
AKI assessment:
• Make sure you know about the renal effects of all drugs taken
• Assess volume status — check BP, JVP, skin turgor, capillary refill (<2s), urine output (catheterize).
• Check an urgent K+ on a venous blood specimen and an ECG to check for life- threatening hyperkalaemia
Michael Grant
lOMoARcPSD|4927727

• History: check for risk factors (see BOX), comorbidities, ask about previous renal disease
• Examination: Full systemic examination. Specific features to look for include a palpable bladder, palpable kidneys (polycystic disease),
abdominal/pelvic masses, renal bruits (signs of renovascular disease), rashes.
• Bedside tests: Always, always dip the urine. See p236. Dipstick can suggest infection (leucocytes + nitrites), glomerular disease (blood +
protein). Microscopy for casts, crystals and cells
• Blood tests: U&E, FBC, LFT, clotting, CK, ESR, CRP, consider ABG for acid base assessment, autoantibodies (ANCA, ANA, anti-GBM)
• Monitoring: Consider transfer to intensive care or high-dependency unit (ICU/HDU). • Check pulse, BP, JVP, and urine output hourly (insert
a urinary catheter). Consider inserting a CVP line if on HDU/ICU.
AKI Management:
• See GAIN algorithm below
• Manage complications: hyperkalaemia, pulmonary oedema, uraemia, acidaemia
• Consider Renal replacement therapy - options in AKI include haemodialysis and haemofiltration, both require large-bore venous
access (e.g. internal jugular line)
o A ICU are often filtered, as the fluid shifts are much less significant and therefore BP is less likely to drop. However, filtration
is much slower at clearing solutes, and is usually performed continuously
Acute tubular necrosis is a condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys.
• ATN presents with acute kidney injury (AKI) and is one of the most common causes
• Common causes of ATN include low blood pressure (75% of cases) and use of nephrotoxic drugs.
• The presence of "muddy brown casts" of epithelial cells found in the urine during urinalysis is pathognomonic for ATN
• Tubules regulate salt and water reabsorption thus failure results in:
o Non-concentration of urine with low osmolality
o Urine [Na+] high (> 20 mmol/l)
Definitions
• Oliguria:
§ < 400-500 mls/day
§ < 0.5ml/kg/hr
§ < 20-30 mls/hr for most adults
• Anuria: absence of urine output
Michael Grant
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Chronic renal failure is defined as Impaired renal function for >3 months
based on abnormal structure or function, or GFR <60mL/min/1.73m2
for >3 months with or without evidence of kidney damage
• Symptoms usually only occur once stage 4 is reached (GFR <30)
• End-stage renal failure (ESRF) is defined as GFR <15 mL/min/1.73m2
or need for renal replacement therapy (RRT—dialysis or transplant).
Causes of chronic kidney disease:
1. Diabetic nephropathy
2. Hypertensive renal vascular disease
3. Glomerulonephritis
4. Polycystic kidney disease
• History with patient with known/suspected CKD, try to identify:
o Possible cause: ask about previous UTIS, LUTS (lower urinary tract symptoms)
o PMH of BP, DM, IHD, systemic disorder, renal colic
• Examination for examining patients with known CKD.
o First presentation: pallor, uraemic tinge to the skin (yellowish), purpura,
excoriations, BP, cardiomegaly, signs of fluid overload, possible cause (eg
ballotable polycystic kidneys)
o Known CKD/ESRF:
§ Cause of ESRF/CKD, eg polycystic kidneys, signs of IHD, DM
§§Current mode of renal replacement therapy (RRT) and any
complications, eg transplant + skin malignancy from immunosuppression
§ Previous types of RRT and any complications, e.g. arteriovenous
fistula + parathyroidectomy scar (normalization or stabilization of
calcium and parathyroid hormone (PTH) metabolism, and for
improving renal osteodystrophy)
§ Face: Pallor of anaemia, yellow tinge of uraemia, gum hypertrophy
from ciclosporin, cushingoid appearance from steroids.
§ Neck: Tunnelled line insertion (Small scar over internal
jugular, and a larger scar in ‘breast pocket’ area from the exit
site)
§ Abdo: signs of previous transplant (hockey-stick scar,
palpable mass), ballotable polycystic kidneys ± liver.
• Tests:
o Blood: Hb (normochromic, normocytic anaemia), ESR, U&E,
glucose (DM), low Ca2+, high PO43– & alk phos (renal
osteodystrophy – raised PTH if stage 3)
o Imaging: USS to check size, anatomy and corticomedullary
differentiation
§ In CKD kidneys are usually small (<9cm) but can be enlarged in infiltrative disorders (amyloid, myeloma), APKD
o Histology: Consider renal biopsy if rapidly progressive disease or unclear cause and normal sized
§ Indications for renal biopsy: Unexplained acute kidney injury or chronic kidney disease, acute nephritic syndromes
§ Contraindications: •Abnormal clotting •Hypertension >160/>90mmHg •Single kidney (except for renal transplants) • Chronic
kidney disease with small kidneys (<9cm)
§ Post-procedure: Bed rest for a minimum of 6h. Monitor pulse, BP, symptoms, and urine colour. Bleeding is the main
complication
• Management:
o Identify and treat reversible causes: obstruction, stop nephrotoxic drugs, fluid balance, cardiovascular risk (SALAD)
o Limit progression:
§ BP: aim for <130/80 and in diabetics even with normal BP treat with ACE-I and ARB to limit progression
§ Renal bone disease: measure PTH and treat, restrict, give binders (calcichew), diet (healthy, moderate protein diet, K+ restriction
if hyperkalaemic, and avoidance of high phosphate foods)
o Symptom control:
§ Anaemia – replace iron/B12/folate if necessary; if still anaemic
consider recombinant human erythropoietin
• Hb falls despite this, and no infection,
haemolysis, or blood loss, etc. suspect red
cell aplasia (anti-epo antibodies)
§ Acidosis – sodium bicarb supplements (may also slow progression)
§ Oedema – high doses of loop diuretics, restriction on fluid and Na
intake
§ Restless legs – check ferritin (low worsens symptoms), gabapentin may
help
o Preparation for renal replacement:
§ Haemodialysis (HD) Blood is passed over a semi-permeable
membrane against dialysis fluid flowing in the opposite direction, thus
blood passes solutes by concentration gradient with ultrafiltration
creating a negative pressure used to clear excess fluid
Michael Grant
lOMoARcPSD|4927727

• Problems: Disequilibration syndrome, hypotension, time consuming, access problems
o AV fistula: thrombosis, stenosis, steal syndrome
o Tunnelled venous access line (duel lumen): infection, blockage, recirculation of blood
§ Haemofiltration Blood is filtered across a
highly permeable membrane, allowing
movement of large and small solutes by
convection at almost the same rate. The
ultrafiltrate is replaced with an equal volume of
fluid, so there is less haemodynamic instability.
It is used in critically ill patients for this reason.
§ Peritoneal dialysis (PD) Uses the peritoneum
as a semi-permeable membrane. A Tenckhoff
catheter is inserted into the peritoneal cavity
and fluid infused, allowing solutes to di use
slowly across. Ultrafiltration can be achieved
by adding osmotic agents such as glucose to
the fluid. It is simple to perform, can be carried
out continuously and at home, and so allows
the patient more freedom
• Problems: PD
peritonitis, exit site infection, loss of membrane function over time (becomes fibrotic)
§ Complications:
• Annual mortality is ~20%, mostly due to cardiovascular disease: MI and CVA are much commoner in
dialysis patients
• Renal bone disease: high bone turnover, renal osteodystrophy and osteitis fibrosa (due to high PTH)
• Infection: Uraemia causes granulocyte dysfunction
• Amyloid accumulates in long–term dialysis patients
1. Diabetic nephropathy
• Early on, glomerular and tubular hypertrophy occur, increasing GFR transiently,
but ongoing damage from AGE products triggers more destructive disease. These
AGE trigger an inflammatory response leading to deposition of type IV
collagen and mesangial expansion, eventually leading to arterial hyalinization,
thickening of the mesangium and glomerular basement membrane and nodular
glomerulosclerosis (Kimmelstiel–Wilson lesions). Progression generally occurs in
four stages:
o GFR elevated: early in disease renal blood flow increases, increasing the GFR
and leading to microalbuminuria. As sugars are controlled, this falls back to
normal
o Glomerular hyperfiltration: in the next 5–10yrs mesangial expansion
gradually occurs and hyperfiltration at the glomerulus is seen without microalbuminuria
o Microalbuminuria: as soon as this is detected it indicates progression of disease, GFR may be raised or normal. This lasts another 5–
10yrs
o Nephropathy: GFR begins to decline and
proteinuria increases.
2. Hypertensive renal vascular disease is one of the

leading causes of CKD due to the deleterious effects that
increased BP has on kidney vasculature. Long-term,
uncontrolled, high BP leads to high intraglomerular
pressure, impairing glomerular filtration. Damage to the
glomeruli lead to an increase in protein filtration, resulting
in abnormally increased amounts of protein in the urine
(microalbuminuria or proteinuria).
3. Glomerulonephritis
• Glomerulonephritis alters the properties of the GBM
leading to protein loss from the circulation into the
urine space (proteinuria). If the barrier is severely
disrupted red cells may enter the urine
• Glomerulonephritis simply means inflammation of
the glomeruli and nephrons; when you remember
this you can appreciate what the consequences of
this inflammation are:
o Damage to the glomerulus restricts blood
flow, leading to compensatory raised BP
o Damage to the filtration mechanism allows protein
and blood to enter the urine
Michael Grant
lOMoARcPSD|4927727

o Loss of the usual filtration capacity leads to acute kidney injury
• Depending on the degree of inflammation and damage, therefore there is a spectrum of disease:
o Blood pressure: normal to malignant hypertension
o Urine dipstick:
§ Proteinuria - mild is nephrotic syn
§ Haematuria - mild/macroscopic is nephritic syn
o Renal function: normal to severe impairment
• Variable clinical presentation
o Asymptomatic - identified on screening
o Frank haematuria
o Hypertension
o Proteinuria --> nephrotic
syndrome
o Post-infectious illness
o Acute kidney injury-->
‘nephritic’ syndrome
o Chronic kidney disease
• Examination:
o Blood pressure
o Presence of oedema
o Urinalysis
• Tests:
• Blood: FBC, U&E, LFT, ESR, CRP; immunoglobulins, electrophoresis,
complement (C3, C4); autoantibodies: ANA, ANCA, anti-dsDNA, anti-
GBM; blood culture, ASOT, HBsAg, anti-HCV
• Urine: RBC casts, MC&S, Bence Jones protein, ACR
• Biopsy: immunofluorescence (deposition of Igs, complement,
immune complexes or pauci immune [form of vasculitis that is
associated with minimal evidence of hypersensitivity upon
immunofluorescent staining for IgG]) and electron microscopy
4. Polycystic kidney disease
Michael Grant
lOMoARcPSD|4927727

• A clonal disorder of epithelial cell growth, result from gene products of PKD1 (chr. 16) and PKD2 (chr. 4) which are components of the
same signaling pathway
• Inactivation of two copies of a PKD gene through germline (inherited)
and somatic (acquired) mutations within an epithelial cell confers growth
advantage permitting formation of a cyst with somatic mutation is the rate-
limiting step
• What is Autosomal dominant PKD?
o Positive USS
§ < 30 yo – at least 2 cysts (unilateral or bilateral)
§ 30-59 yo – at least 2 cysts in each kidney
§ > 60 yo – at least 4 cysts in each kidney
• Renal manifestations of ADPKD
o Haematuria
o Flank and abdominal pain
§ Pain may be helped by laparoscopic cyst removal or
nephrectomy, control water intake, Na+ intake
o Nephrolithiasis (renal stones)
o Hypertension
§ Should be treated aggressively, with target levels of
<130/80mmHg (ACE-i are best choices)
o Chronic kidney disease
o Anaemia
o Asymptomatic and identified on scan
• Extrarenal features (mostly produced due to abnormal collagen):
o SAH from aneurysms in the circle of willis (10-15%)
§ Screening for SAH with magnetic resonance angiography may be
done in 1st-degree relatives of those with SAH + ADPKD
o Aortic aneurysms
o Hepatic cysts
o Colonic diverticulae
o Abdominal and inguinal hernias
o Mitral valve prolapse
• Treat infections, dialysis or transplantation for ESRF, genetic counselling
• Around 50% will be in end-stage kidney disease and require dialysis or
transplantation by the age of 60 in PKD1 and the age of 75 in PKD2
Renal artery stenosis is stenosis of the renal artery or one of its branches
• Causes: Atherosclerosis (80%), fibromuscular dysplasia (10%, younger). Rarer: Takayasu’s
arteritis, antiphospholipid syndrome, post-renal transplant, thromboembolism, external
compression
• Signs: BP resistant to treatment; worsening renal function after ACE-i/ARB in bilateral
renal artery stenosis; ‘flash’ pulmonary oedema (sudden onset, without LV impairment on
cardiac echo), Abdominal ± carotid or femoral bruits
• Tests: USS: renal size asymmetry (affected side is smaller), disturbance in renal blood flow
on Doppler, Renal angiography is ‘gold standard’, but do after CT/MR as it is invasive
• Treatment: Comprehensive antihypertensive regimens, transluminal angioplasty ± stent
placement
Michael Grant
lOMoARcPSD|4927727

Acid/base balance disorders (see POEM notes)
Michael Grant
lOMoARcPSD|4927727

Transplant
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis
or fulminant liver failure
• Three major components: Cirrhosis + ascites + renal failure ≈ HRS — if
other causes of renal impairment have been excluded.
• Abnormal haemodynamics causes splanchnic and systemic
vasodilatation, but renal vasoconstriction.
• Bacterial translocation, cytokines and mesenteric angiogenesis cause
splanchnic vasodilatation, and altered renal autoregulation is involved
in the renal vasoconstriction.
• Types of HRS:
o HRS 1 is a rapidly progressive deterioration in circulatory and renal
function (median survival <2wks), often triggered by other
deteriorating pathologies. Terlipressin replenishes hypovolaemia.
Haemodialysis may be needed
o HRS 2 is a more steady deterioration (survival ~6 months).
Transjugular intrahepatic portosystemic stent shunting is the best
Michael Grant
lOMoARcPSD|4927727

option for most (TIPS - hunts blood away from the portal circulation through an artificial side-to-side porto–systemic anastomosis in
the liver; also used in uncontrolled variceal haemorrhage)
§ Other factors in cirrhosis may contribute to poor renal
function
• Transplants Liver transplant may be required. After >8–12wks of pre-
transplant dialysis, some may be considered for combined liver-kidney
transplantation
Nephrotic syndrome is a triad of:

o Proteinuria >3.5g/24h (ACR
>250mg/mmol)
o Hypoalbuminaemia (<25g/L, usually much
lower)
o Oedema
• Causes:
o Primary causes: Minimal change disease,
membranous nephropathy, focal
segmental glomerulosclerosis (FSGS),
mesangiocapillary GN (MCGN)
o Secondary causes: Hepatitis B/C (usually
membranous, hep C can cause MCGN),
SLE (class V lupus nephritis causes a
membranous pattern), diabetic nephropathy, amyloidosis, paraneoplastic
(usually membranous pattern) or drug related (again usually membranous—
NSAIDS)
• Assessment: Patients present with pitting oedema, occurring in dependent
areas and areas of low tissue resistance, eg periorbitally.
• History: Ask about acute or chronic infections, drugs, allergies, systemic
symptoms suggestive of autoimmunity or malignancy
• Signs: Urine dip shows ++++ protein, albumin is low, BP is usually normal or
mildly increased, renal function is usually normal or mildly impaired
• Differential diagnosis: CCF (JVP, pulmonary oedema, mild proteinuria) or
liver disease (low albumin)
• Complications
o Susceptibility to infection (eg cellulitis, Streptococcus infections and
spontaneous bacterial peritonitis) happens in up to 20% of adult patients
because of low serum IgG, low complement activity, and reduced T cell
function (due in part to loss of immunoglobulin in urine and also to
immunosuppressive treatments).
o Thromboembolism: (Up to 40%): eg DVT/PE, renal vein thrombosis. This
hypercoagulable state is partly due to rise in clotting factors and platelet
abnormalities.
o Hyperlipidaemia: High cholesterol and triglycerides, thought to be due to hepatic lipoprotein synthesis in response to low oncotic
pressure.
• Treatment
o 1 Reduce oedema: Loop diuretics, eg furosemide are used, often high doses
are needed. Gut oedema may prevent oral absorption so IV route is useful.
Check daily weight (aim for 0.5–1kg loss/day) and daily U&Es. Fluid restrict to
1L/day and salt restrict while giving diuretics.
o 2 Reduce proteinuria: ACE-i or ARB should be started in all patients.  
Michael Grant
lOMoARcPSD|4927727

o 3 Reduce risk of complications: Anticoagulate if nephrotic range proteinuria, start a statin to reduce cholesterol (although often
resolves spontaneously when cause treated), treat infections promptly and vaccinate
o 4 Treat underlying cause
Gastrointestinal
Irritable Bowel Syndrome
Aetiology:
• There is no structural lesion, and no single explanation has
been found to explain the condition. However, it seems to
involve abnormal smooth muscle activity ± visceral
hypersensitivity, and abnormal central processing of painful
stimuli.
• Presents at <40yo and 2:1 F:M
• There is evidence of abnormal bowel transit time
• Balloon distension of the bowel in affected individuals leads to
perception of pain at lower thresholds than those without it
• Subclasses of IBS have been identified as follows:
o Approximately one third of patients have IBS with
constipation (IBS-C) = loose stools <25% and hard stools
>25% of the time.
o Approximately one third of patients have IBS with diarrhoea
(IBS-D) = loose stools >25% and hard stools <25% of the
time.
o The remainder have IBS-mixed (IBS-M) = both hard and soft stools >25% of the time
Presentation:
• National Institute for Health and Care Excellence (NICE) positive diagnostic criteria for IBS; Patients must give at least a six-month
history of either:
o Abdominal pain or discomfort.
o Bloating.
o Change in bowel habit.
• Consider positively diagnosing IBS only if abdominal pain is either relieved by defecation, or associated with altered bowel
frequency or stool form; AND at least 2 of the following are present:
o Altered passage of stool (straining, urgency, incomplete evacuation).
o Abdominal bloating (women >men), distention tension or hardness – may be tender on examination
o Symptoms aggravated by eating
o Passage of mucus rectally.
Investigations:
All patients meeting the symptomatic criteria for IBS should have the following investigations:
• FBC
• ESR
• CRP
• Coeliac screen
• CA 125 for women with symptoms which could
• Faecal calprotectin for those with symptoms which could be IBD
Refer to specialist if there are red flag symptoms
Treatment is rarely 50% successful, so aim to make symptoms less intrusive by forging a therapeutic alliance
• Ensure a healthy diet; fibre, lactose, fructose, wheat, starch, caffeine, sorbitol, alcohol and fizzy drinks may worsen symptoms
• Probiotics and water-soluble fibre may be OK.
• Constipation: fibre intake can worsen flatulence/bloating; avoid insoluble fibre, such as bran (oats are better). Bisacodyl and
sodium picosulfate233 can help constipation.
• Diarrhoea: Avoid sorbitol sweeteners; try a bulking agent ± loperamide 2mg after each loose stool; max 16mg/d (NNT=5); SE:
colic, bloating, ileus
• Colic/bloating: Oral antispasmodics: mebeverine 135mg/8h (over the counter)
• Psychological symptoms/visceral hypersensitivity: Emphasize the positive! In 50% symptoms go or improve after 1yr; <5% worsen so
consider cognitive behaviour therapy
Stomach cancer is on the decline in the west, but is still relevant due to its complications and mortality.
• There are two types:
o Intestinal type
§ Forms glands
§ Older age group >50yo esp. males
§ Appears as either an exophytic mass or malignant ulcer
§ Usually located in body, antrum or cardia
Michael Grant
lOMoARcPSD|4927727

o Diffuse type
§ Do not form acini
§ Earlier age group, equal gender distribution
§ Does not form a discreet mass but causes a diffuse thickening and rigidity
(known as linitis plastica – which resists inflation on OGD)
§ Presents of signet ring cell
o Gastric lymphoma
§ Is linked to chronic infection by H. Pylori which causes lymphoid tissue to
migrate to the gastric mucosa (becoming a form of MALT)
§ Lymphoid proliferation is antigen dependant and polyclonal in reactive to
the bacteria
§ The persistence of the H. Pylori infection causes the formation of a MALToma
that is malignant:
• Causes destruction of gastric glands with lymphoepithelial lesions (lymphocytes burrow into epithelium)
• May be presence of monoclonal B-cells
• Even though it may be neoplastic B-cell, the proliferation is still dependant on T-cell anti-gen presentation for activation thus
treating H. Pylori can cause regression
• Risk factors:
o Diet (high nitrates, low fresh veg.)
o H. Pylori
o Atrophic gastritis
o Gastric surgery
o E-Cadherin mutations (typically in diffuse type)
o Weight loss/anorexia
o Virchows nodes
o Krekenberg tumours are bilateral ovarian tumours due to direct mets (usually from diffuse type)
• Prognosis is poor (<20% 5ys)
• Surgery Localized disease may be treated by curative gastrectomy, either D1 resection (excision of tumour and perigastric nodes) or D2
resection (basically a D1 resection extended to include nodes around the coeliac axis):
o Billroth I: Partial gastrectomy with simple gastroduodenal re-anastomosis
o Billroth II: (aka Polya) gastrectomy (fig 1) Partial gastrectomy with gastrojejunal anastamosis. The duodenal stump is oversewn
(leaving a blind afferent loop)
o Roux-en-Y: - Following total or subtotal gastrectomy, the proximal duodenal stump is oversewn, the proximal jejunum is divided from
the distal duodenum and connects with the oesophagus (or proximal stomach after subtotal gastrectomy) whilst the distal duodenum
is connected to the distal jejunum.
Hiatus hernia
• Sliding hiatus hernia (80%) is where the gastro-oesophageal junction slides
up into the chest; Acid reflux often happens as the lower oesophageal
sphincter becomes less competent in many cases.
• Rolling hiatus hernia (20%) is where the gastro-oesophageal junction
remains in the abdomen but a bulge of stomach herniates up into the
chest alongside the oesophagus.
o As the gastro-oesophageal junction remains intact, gross acid reflux is
uncommon
o Risk of strangulation to stomach tissue in hernia
• Common: 30% of patients >50yrs, especially obese women. 50% have
symptomatic gastro-oesophageal reflux.
• Imaging Barium swallow is the best diagnostic test; upper GI endoscopy visualizes the mucosa (?oesophagitis) but cannot reliably
exclude a hiatus hernia from inside
• Treatment: Lose weight. Treat reflux symptoms.
• Surgery indications: intractable symptoms despite aggressive medical therapy, complications.
o It is advised to repair rolling hiatus hernia prophylactically (even if asymptomatic) as it may strangulate
o Surgery is usually laproscopic fundoplication
Hepatoma
• The commonest (90%) liver tumours are secondary (metastatic) tumours, eg from breast, bronchus, or the gastrointestinal tract
• Primary hepatic tumours are much less common and may be benign or
malignant (see TABLE)
• Symptoms:
o Fever, malaise, anorexia, weight loss, RUQ pain (liver capsule stretch).
o Jaundice is late, except with cholangiocarcinoma. Benign tumours are
often asymptomatic. Tumours may rupture causing intraperitoneal
haemorrhage.
• Signs:
o Hepatomegaly (smooth, or hard and irregular, eg metastases, cirrhosis,
HCC)
o Look for signs of chronic liver disease and evidence of decompensation (jaundice, ascites)
Michael Grant
lOMoARcPSD|4927727

o Listen for a bruit over the liver (HCC)
o Tests:
§ Blood: FBC, clotting, LFT, hepatitis serology, alpha-fetoprotein1
§ Imaging: US or CT to identify lesions and guide biopsy (careful as seeding along the
biopsy tract can occur). MRI is better at distinguishing benign from malignant lesions.
• Do ERCP and biopsy if cholangiocarcinoma is suspected.. If the lesion could be
a metastasis, find the primary, eg by CXR, mammography, endoscopy,
colonoscopy, CT, MRI, or marrow biopsy.
• Liver metastases signify advanced disease. Treatment and prognosis vary with
the type and extent of primary tumour.
• Hepatocellular carcinoma (HCC) Primary hepatocyte neoplasia accounts for 90% of primary
liver cancers; it is common in China & Africa (40% of cancers vs 2% in UK)
o Causes: HBV is the leading cause, HCV; AIH; cirrhosis (alcohol, haemochromatosis,
PBC); non-alcoholic fatty liver; aflatoxin (sun dried maize); anabolic steroids
o Tests: 4-phase CT (delayed wash-out of contrast in a suspect mass); MRI; biopsy
o Treatment: Resecting solitary tumours <3cm across; but ~50% have recurrence by
3yrs.3 Liver transplant gives a 5yr survival rate of 70%.
§ Percutaneous ablation, tumour embolization (TACE5), and sorafenib are options.
• Cholangiocarcinoma (biliary tree cancer); ~10% of liver primaries.
o Causes: Flukes (Clonorchis - Chinese liver fluke); PSC (screening by CA19-9 may be
helpful); biliary cysts; Caroli’s disease (inherited disorder characterized by dilation of
the intrahepatic bile ducts – can lead to portal hypertension and fibrosis); HBV; HCV; DM
o The patient: Fever, abdominal pain (± ascites), malaise, raised bilirubin and alk phos
o Pathology: Usually slow-growing. Most are distal extrahepatic or perihilar (be aware of
Catskin type)
o Management: 70% are unsuited to surgery (76% recur for those that can have surgery)
§ Surgery: eg major hepatectomy + extrahepatic bile duct excision + caudate lobe
resection. 5yr survival is ~30%.
§ Post-op complications include liver failure, bile leak and GI bleeding
§ Stenting of an obstructed extrahepatic biliary tree, percutaneously or via
ERCP, improves quality of life.
§ Prognosis: ~5 months
• Benign tumours
o Haemangiomas are the commonest benign liver tumours. They are often an incidental
finding on ultrasound or CT and don’t require treatment. Avoid biopsy!!
o Adenomas are common. Causes: Anabolic steroids, oral contraceptive pill; pregnancy.
Only treat if symptomatic, or >5cm.
Hepatitis:
Cirrhosis (Greek kirrhos = yellow) implies irreversible liver damage
• Histologically: bridging fibrosis and nodular regeneration
• Causes:
o Most often chronic alcohol abuse, HBV, or HCV infection.
• Signs: May be none (just abnormal LFT) or decompensated end-stage liver disease
• Chronic liver disease:
o Nails/Hands: Leuconychia: white nails with lunulae undemarcated, from
hypoalbuminaemia; Terry’s nails—white proximally but distal 1⁄3 reddened by
telangiectasias; clubbing; palmar erythema; hyperdynamic circulation;
Dupuytren’s contracture
o General: Spider naevi; xanthelasma; gynaecomastia; atrophic testes (?reduction in
albumin); loss of body hair; parotid enlargement; hepatomegaly, or small liver in late disease
• Complications:
o Hepatic failure: Coagulopathy (reduction in factors II, VII, IX, & X causes high INR); encephalopathy—ie liver flap (asterixis) +
confusion/coma; hypoalbuminaemia (oedema, leuconychia); sepsis (pneumonia; septicaemia); spontaneous bacterial peritonitis
(SBP) – ?impaired airport security function of Kupfner cells; hypoglycaemia
o Portal hypertension: Ascites; splenomegaly; portosystemic shunt including oesophageal varices (± life-threatening upper GI bleed)
and caput medusae (enlarged superficial periumbilical veins)
o Increased risk of HCC
Autoimmune hepatitis (AIH) is an inflammatory liver disease of unknown cause

characterized by suppressor T-cell defects with autoantibodies directed against
hepatocyte surface antigens
• Classification is by autoantibodies (see TABLE)
• AIH predominantly affects young or middle-aged women (bimodal, ie 10–30yrs—
or >40yrs old)
• Up to 40% present with acute hepatitis and signs of autoimmune disease, eg fever,
malaise, urticarial rash, polyarthritis, pleurisy, ? hypersplenism, pulmonary
infiltration, or glomerulonephritis
• Complications: Those associated with cirrhosis and drug therapy.
Michael Grant
lOMoARcPSD|4927727

• Tests: hypergammaglobulinaemia (esp. IgG), +ve autoantibodies (see TABLE)
o Liver biopsy: mononuclear infiltrate of portal and periportal areas and piecemeal necrosis ± fibrosis
o MRCP helps exclude PSC if alk phos disproportionately rasied
§ PSC seen with multiple segmental strictures, biliary dilatation, biliary diverticula
• Diagnostic criteria based on IgG levels, autoantibodies, and histology in the absence of viral disease
• Management:
o Immunosuppressant therapy: Prednisolone 30mg/d PO for 1 month; Azathioprine (50–100mg/d PO) steroid-sparing agent to
maintain remission.
o Liver transplantation is indicated for decompensated cirrhosis,
but recurrence may occur.
Non-alcoholic fatty liver disease (NAFLD)

• Fatty hepatocytes (steatosis) ± inflammation (steatohepatitis) seen on
ultrasound; consider NAFLD if they drink <18U/wk (<9U in women)
• It may (rarely) progress to hepatic fibrosis ± hepatocellular cancer (all-
cause mortality is hardly aff ected)
• Typical patient: Middle-aged obese with factors such as: DM;
dyslipidaemia; parenteral feeding; jejuno–ileal bypass; Wilson’s disease;
drugs (eg amiodarone, methotrexate, tetracycline)
o Biopsy may be needed
• Treatment: Control risk factors. Bariatic surgery helps. No drug is of
proven benefit. Follow-up: LFT; glucose.
Wilson’s disease is a rare (3/100,000) inherited disorder of biliary copper

excretion with too much copper (Cu) in liver and CNS (basal ganglia, eg globus pallidus hypodensity ± putamen cavitation).
• Autosomal recessive disorder of a gene on chromosome 13 that codes for a copper transporting ATPase, ATP7B
• In the liver, copper is incorporated into caeruloplasmin. Intestinal copper absorption and transport into the liver are intact, while copper
incorporation into caeruloplasmin in hepatocytes and its excretion
into bile are impaired. Therefore, copper accumulates in liver, and
later in other organs.
• Signs:
o Children present with liver disease (hepatitis, cirrhosis, fulminant
liver failure);
o Young adults often start with CNS signs - tremor; dysarthria,
dysphagia; dyskinesias; dystonias; purposeless stereotyped
movements (eg hand clapping); dementia; parkinsonism;
micrographia; ataxia/clumsiness
o Mood: Depression/mania; labile emotions; libido down; personality
change
o Cognition: Memory; quick to anger; slow to solve problems; IQ
o Kayser–Fleischer (KF) rings: Copper in iris
o Also: Haemolysis; blue lunulae (nails); arthritis; hypermobile joints;
grey skin.
• Tests: Equivocal copper studies need expert interpretation.
o Urine: 24h copper excretion is high
o LFT : Non-specific (but ALT >1500 is not part of the picture).
o Serum copper: Typically <11μmol/L.
o Serum caeruloplasmin฀: <200mg/L (<140mg/L is pathognomonic).
§ Falsely low caeruloplasmin: Protein-deficiency states (eg nephrotic syndrome, malabsorption);
§ Falsely high caeruloplasmin: Caeruloplasmin is an ‘acute phase reactant’, so sometimes high in inflammation/infection
o MRI: Degeneration in basal ganglia, fronto-temporal, cerebellar and brainstem
• Management:
o Diet: Avoid eating foods with a high copper content (eg liver, chocolate, nuts, mushrooms, legumes, and shellfish)
o Drugs: Lifelong penicillamine; SE: nausea, rash, haematuria, nephrosis, lupus. Monitor FBC and urinary Cu and protein excretion.
Haemochromatosis is an inherited disorder of iron metabolism in

which increases intestinal iron absorption leads to iron deposition in
joints, liver, heart, pancreas, pituitary, adrenals and skin
• Middle-aged men are more frequently and severely affected than
women, in whom the disease tends to present ~10yrs later
(menstrual blood loss is protective)
• Common inherited Northern European (especially Celtic)
ancestry (carrier rate of ~1 in 10) with the gene responsible for
most HH is called HFE, found on the short arm of chromosome 6
• Early on: Nil—or tiredness; arthralgia (2nd+3rd MCP joints +
knee pseudogout)
• Later: Slate-grey skin pigmentation; signs of chronic liver
disease; hepatomegaly; cirrhosis; dilated cardiomyopathy;
Michael Grant
lOMoARcPSD|4927727

• Endocrinopathies: DM (‘bronze diabetes’ from iron deposition in pancreas); hypogonadism from pituitary dysfunction
• Tests:
o Blood: LFT, serum ferritin (>1mg/L is very suggestive, but any inflammatory process can
raise ferritin); transferrin saturation >45%.1 Glucose (?DM)
o HFE genotype
o Images: Chondrocalcinosis (Calcium pyrophosphate dihydrate (CPPD) crystal deposition
disease, also known as pseudogout)
o Liver MRI: Fe overload (sensitivity 84–91%)
o Liver biopsy: Perl’s stain quantifies iron loading and assesses disease severity
• Management: Venesect ~1 unit/1–3wks, until ferritin 50μg/L (may take 2yrs) - maintenance
venesection is needed for life
o Over-the-counter drugs: Ensure vitamin preparations etc contain no iron.
o Diet: A well-balanced low-iron diet may help. Tea, coffee or red wine with meals reduceiron
absorption, but fruit/fruit juice (high in vit. C) and white wine increase absorption
• Secondary haemochromatosis may occur if many transfusions (~40L in total) have been given
Viral hepatitis
• Hepatitis A RNA virus. Spread: Faecal–oral or shellfish.
o Incubation: 2–6wks
o Symptoms: Fever, malaise, anorexia, nausea, arthralgia—then: jaundice (rare in children)
hepatosplenomegaly, and adenopathy
o Tests: AST and ALT rise 22–40d after exposure (ALT may be >1000u/L), IgM rises from day
25 and means recent infection. IgG is detectable for life.
o Treatment: Supportive. Avoid alcohol. Rarely, interferon – for fulminant hepatitis
o Active immunization is with Havrix Monodose®, an inactivated protein derived from HAV
o Prognosis: Usually self-limiting. Fulminant hepatitis is rare. Chronicity doesn’t occur.
• Hepatitis B virus (HBV, a DNA virus.)
o Spread: Blood products, IV drug abusers (IVDU), sexual, direct contact
o Incubation: 1–6 months.
o Signs: Resemble hepatitis A but arthralgia and urticaria are
commoner. 
o Tests: HBSAg (surface antigen) is present 1–6 months after exposure.
§ HBeAg (e antigen) is present for 11⁄2–3 months after acute illness
and implies high infectivity.
§ HBSAg persisting for >6 months defines carrier status and
occurs in 5–10% of infections
§ Antibodies to HBCAg (anti-HBc) imply past infection; antibodies
to HBSAg (anti-HBs) alone imply vaccination.
§ HBV PCR allows monitoring of response to therapy
o Vaccination: Passive immunization (specific anti-HBV immunoglobulin)
may be given to non-immune contacts after high-risk exposure. ฀:
o Avoid alcohol. Immunize sexual contacts.
o Refer all with chronic liver inflammation for antivirals, eg pegylated
(PEG) interferon alfa-2a, lamivudine, entecavir,189 adefovir.
o The aim is to clear HBSAg and prevent cirrhosis and HCC (risk is ฀฀
if HBSAg and HBeAg +ve)
o Other complications: fulminant hepatic failure, cholangiocarcinoma,
cryoglobulinaemia (cryoglobulins – proteins that become insoluble at
reduced temperatures)
• Hepatitis C virus (HCV) RNA flavivirus
o Spread: Blood: transfusion (thousands of UK cases;
compensation is available), IV drug abuse, sexual,
acupuncture.
o Early infection is often mild/asymptomatic. ~85%
develop silent chronic infection; ~25% get cirrhosis in
20yrs—of these, 4% get hepatocellular cancer (HCC)/yr.
o HCV is the chief reason for liver transplant in the West. 
o Risk factors for progression: Male, older, higher viral
load, use of alcohol, HIV, HBV.
o Tests: LFT (AST:ALT <1:1 until cirrhosis develops), anti-
HCV antibodies confirms exposure; HCV-PCR
confirms on-going; liver biopsy if HCV-PCR +ve to
assess liver damage;
o Rx: Quit alcohol, serine protease inhibitors boceprevir
and telaprevir are the first in a new class of directly
acting antivirals against genotype 1 hepatitis C (HCV).
When combined with pegylated interferon and ribavirin
Michael Grant
lOMoARcPSD|4927727

o Complications: Glomerulonephritis; cryoglobulinaemia; thyroiditis; autoimmune hepatitis; PAN; polymyositis; porphyria cutanea
tarda (results from low levels of the enzyme responsible for the fifth step in heme production)
• Hepatitis D virus (HDV) is an incomplete RNA virus (needs HBV for its assembly) – HBV vaccination prevents HDV infection
o Tests: Anti-HDV antibody (only ask for it if HBsAg +ve).
o Treatment: As interferon – has limited success, liver transplantation may be
needed
• Hepatitis E virus (HEV) RNA virus. Similar to HAV; mortality is high in pregnancy
and is associated with pigs
o Vaccine is available in China (not Europe).
o Tests: Serology. Treatment: Nil specific. 
• Hepatitis G & GB Parenterally transmitted. No good evidence they damage the
liver.
• Other causes of hepatitis Alcohol; drugs; toxins; EBV/CMV; leptospirosis; malaria;
syphilis; yellow fever; autoimmune hepatitis; Wilson’s
Acute and chronic liver failure

• Liver failure may occur suddenly in the previously healthy liver = acute hepatic
failure. More often it occurs as a result of decompensation of chronic liver disease
= acute-on-chronic hepatic failure.
• Fulminant hepatic failure is a clinical syndrome resulting from massive necrosis
of liver cells leading to severe impairment of liver function: hyperacute =
encephalopathy within 7d of onset of jaundice; acute = within 8–28d; subacute =
within 5–26wks
• Causes:
o Infections: Viral hepatitis (esp B, C, CMV), yellow fever, leptospirosis
o Drugs: Paracetamol overdose, halothane, isoniazid
o Toxins: Amanita phalloides mushroom, carbon tetrachloride.
o Vascular: Budd–Chiari synd., veno-occlusive disease
o Others: Alcohol, primary biliary cirrhosis, haemochromatosis, autoimmune
hepatitis, alpha1-antitrypsin deficiency, Wilson’s disease, fatty liver of
pregnancy, malignancy, HELLP syndrome
• Signs: Jaundice, hepatic encephalopathy, fetor hepaticus (smells like pear
drops), asterixis/flap, constructional apraxia (cannot copy a 5-pointed star?)
• Tests:
o Blood: FBC (?infection, ?GI bleed), U&E,2 LFT, clotting (increased PT/INR),
glucose, paracetamol level, hepatitis, CMV and EBV serology, ferritin,
alpha1-antitrypsin, caeruloplasmin, autoantibodies
o Microbiology: Blood culture; urine culture; ascitic tap for MC&S of ascites—
neutrophils >250/mm3 indicates spontaneous bacterial peritonitis
o Radiology: CXR; abdominal ultrasound; Doppler flow studies of the portal
vein (and hepatic vein in suspected Budd–Chiari syndrome)
o Neurophysiology: EEG, evoked potentials (and neuroimaging)
• Management: Beware sepsis, hypoglycaemia, GI bleeds/varices &
encephalopathy:
o Nurse with a 20° head-up tilt in ITU
o Insert urinary and central venous catheters to help assess fluid status.
o Monitor T°, respirations, pulse, BP, pupils, urine output hourly. Daily weights
and check FBC, U&E, LFT, and INR daily
o Treat the cause, if known (eg GI bleeds, sepsis, paracetamol poisoning)
o Treat seizures with lorazepam
o Consider PPI as prophylaxis against stress ulceration, eg omeprazole
o Bleeding: Vitamin K, platelets, FFP + blood as needed ± endoscopy
o Encephalopathy: Avoid sedatives; 20° head-up tilt in ITU; lactulose and
regular enemas to reduce numbers of nitrogen-forming gut bacteria
Ascites
• To demonstrate ascites elicit signs of a fluid thrill and/or shifting dullness
• Tests: Aspirate ascitic fluid (paracentesis) for cytology, culture, and protein
level (≥30g/L in diseases marked); ultrasound.
Gastroenteritis
• Ask about details of food and water taken, cooking method, time until onset of
symptoms, and whether fellow-diners were affected. Ask about swimming,
canoeing, etc. NB: food poisoning is a notifiable disease
• Tests:
o Stool microscopy/culture if from abroad, an institution, or in day care.
o Usually symptomatic
o Maintain oral fluid intake (±oral rehydration sachets). For severe
symptoms (but not in dysentery), give anti-emetics, eg
prochlorperazine 12.5mg/6h IM + antidiarrhoeals (codeine phosphate
30mg PO/IM or loperamide).
Michael Grant
lOMoARcPSD|4927727

o Antibiotics are only indicated if systemically unwell, immunosuppressed or elderly;
resistance is common.
• Cholera: tetracycline reduces transmission.
• Salmonella: ciprofloxacin 500mg/12h PO, 200–400mg/12h IVI over 60min
• Shigella and Campylobacter: ciprofloxacin as above.
Haematology
Anaemias
Anaemia is defined as a low haemoglobin (Hb) concentration, and may be due either to a low red
cell mass or increased plasma volume (eg in pregnancy).
• May be due to reduced production or increased loss of RBCS and has many causes and requires
history, examination, a nd inspection of the blood film.
• Symptoms: fatigue, dyspnoea, faintness, palpitations, headache,
tinnitus, anorexia—and angina if there is pre-existing disease.
• Signs: pallor (eg conjunctivae)
o In severe anaemia (Hb <80g/L), there may be signs of a
hyperdynamic circulation, eg tachycardia, flow murmurs
(ejection-systolic loudest over apex), and cardiac
enlargement; or retinal haemorrhages (rarely)
• Types of anaemia
o The first step in diagnosis is to look at the mean cell volume
(MCV, normal MCV is 76–96 femtolitres, fL = 1L)
o Low MCV—microcytic anaemia:
§ Iron-deficiency anaemia (IDA, most common cause)
§ Thalassaemia (suspect if the MCV is ‘too low’ for the Hb
level)
§ Sideroblastic anaemia (very rare) – bone marrow
produces ringed sideroblasts rather than healthy red
blood cells; Sideroblasts are atypical, abnormal
nucleated erythroblasts (precursors to mature red
blood cells) with granules of iron accumulated in the
mitochondria surrounding the nucleus
• X-linked sideroblastic anemia: This is the most
common congenital cause of sideroblastic anemia
and involves a defect in ALAS2
• Acquired causes include excessive alcohol use (the
most common cause of sideroblastic anemia),
pyridoxine deficiency, lead poisoning, and copper
deficiency
• Excess zinc can indirectly cause sideroblastic
anemia by decreasing absorption and increasing
excretion of copper
§ NB: the last two are conditions where there is an accumulation of iron, and so tests will show serum iron raised, ferritin raised,
and a low total iron-binding capacity (TIBC)
o Normal MCV (normocytic anaemia)
§ Acute blood loss
§ Anaemia of chronic disease
§ Bone marrow failure (reduced WCC and platelets)
§ Renal failure
§ Hypothyroidism
§ Haemolysis
§ Pregnancy
o High MCV (macrocytic anaemia)
§ B12 or folate deficiency
§ Alcohol excess—or liver disease
§ Reticulocytosis – increase in reticulocytes, larger, immature red blood cell (eg with haemolysis)
§ Cytotoxics, eg hydroxycarbamide
§ Myelodysplastic syndromes
§ Marrow infiltration
§ Hypothyroidism
§ Antifolate drugs (eg phenytoin, methotrexate)
• Haemolytic anaemias do not fit into the above classification as the anaemia may be normocytic or, if there are many young (hence
larger) RBCS and reticulocytes, macrocytic.
o Suspect if there is a reticulocytosis (>2% of RBCS; or reticulocyte count >100≈109/L), mild macrocytosis, haptoglobin (haptoglobin
binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity), bilirubin and
urobilinogen. Often mild jaundice (but no bilirubin in urine as haemolysis causes pre-hepatic jaundice).
Michael Grant
lOMoARcPSD|4927727

• Does he need a blood transfusion? Usually No! Unless there is severe acute anaemia (one review suggests that transfusion is not essential
for most patients unless Hb <70g/L). If there is an acute cause (eg haemorrhage with active peptic ulcer), transfusion up to 80g/L is
sometimes needed. Chronic anaemia is better tolerated, and it is important to ascertain the cause, eg in iron-deficiency anaemia, iron
supplements will raise the haemoglobin in a safer and less costly way.
Iron-deficiency anaemia (IDA) this is common (seen in up to 14% of menstruating women):

• Causes:
o Blood loss, eg menorrhagia or GI bleeding1
o Poor diet may cause IDA in babies or children (but rarely in adults),
those on special diets, or wherever there is poverty.
o Malabsorption (eg coeliac disease) is a cause of refractory IDA.
• Signs:
o Chronic IDA (signs now rare): koilonychia, atrophic glossitis, angular
cheilosis, and, rarely, post-cricoid webs (Plummer-Vinson
syndrome)
• Tests: Microcytic, hypochromic anaemia with anisocytosis (red blood
cells are of unequal size) and poikilocytosis (abnormally shaped red
blood cells)
o Deficiency with no obvious source of bleeding mandates careful GI
workup
• Treatment: Treat the cause. Oral iron, eg ferrous sulfate 200mg/8h PO
o SE: nausea, abdominal discomfort, diarrhoea or constipation, black stools.
o Hb should rise by 10g/L/week, with a modest reticulocytosis
o Continue until Hb is normal and for at least 3 months, to replenish stores
o The usual reason that IDA fails to respond to iron replacement is that the patient has rejected the pills.
The anaemia of chronic disease (secondary anaemia) is the commonest anaemia in hospital patients (the 2nd commonest anaemia, after
IDA, worldwide).
• 3 problems (in which the polypeptide, hepcidin, plays a key role):
o 1 Poor use of iron in erythropoiesis
o 2 Cytokine-induced shortening of RBC survival
o 3 Production of and response to erythropoietin
• Causes: Many, eg chronic infection, vasculitis, rheumatoid, malignancy, renal failure.
• Tests: Mild normocytic anaemia (eg Hb >80g/L), ferritin normal, TIBC normal or low. Do blood film, B12, folate, TSH and tests for
haemolysis as anaemia
• Treatment: Treating the underlying disease more vigorously may help:
o Erythropoietin is effective in raising the haemoglobin level (SE: flu-like symptoms, hypertension, mild rise in the platelet count and
thromboembolism)
o It is also effective in raising Hb and improving quality of life in those with malignant disease.5 Iron given parenterally can safely
overcome the functional iron deficiency. Inhibitors of hepcidin and inflammatory modulators show promise.6
Sideroblastic
Microcytic anaemia does not equal iron deficiency! 20% of older people with an MCV <75fL are not iron deficient. Think of sideroblastic
anaemia whenever a microcytic anaemia is not responding to iron.
• Do a ferritin; look at a film (hypochromia) and a marrow to look for disease defining sideroblasts.
• Treament: Remove the cause. Pyridoxine may help ± repeated transfusion for severe anaemia
Macrocytic anaemia (MCV >96fL) is common, often due to alcohol excess without any accompanying anaemia. Although only ~5% are due
to B12 deficiency, pernicious anaemia is the most common cause of a macrocytic anaemia in Western countries.
• A megaloblast is a cell in which nuclear maturation is delayed compared with the cytoplasm. This occurs with B12 and folate
deficiency, as they are both required for DNA synthesis.
• Causes of macrocytosis:
o Megaloblastic: B12 deficiency, folate deficiency, cytotoxic drugs
o Non-megaloblastic: Alcohol, reticulocytosis (e.g. in haemolysis), liver
disease, hypothyroidism, pregnancy
o Other haematological disease: Myelodysplasia, myeloma,
myeloproliferative disorders, aplastic anaemia.
• Tests: B12 and folate deficiency result in similar blood film and bone
marrow biopsy appearances
o Blood film: Hypersegmented polymorphs in B12 and folate deficiency
o Other tests: LFT (include GGT), TFT, serum B12 and serum folate (or
red cell folate—a more reliable indicator of folate status, as serum
folate only reflects recent intake)
o Bone marrow biopsy is indicated if the cause is not revealed by the
above tests. It is likely to show one of the following 4 states:
1 Megaloblastic
2 Normoblastic marrow (e.g. in liver disease, hypothyroidism)
3 Abnormal erythropoiesis (e.g. sideroblastic anaemia, leukaemia, aplasia)
4 Increased erythropoiesis (e.g. haemolysis).
Michael Grant
lOMoARcPSD|4927727

Folate is found in green vegetables, nuts, yeast and liver; it is synthesized by gut bacteria.
Body stores can last for 4 months.
• Maternal folate deficiency causes fetal neural tube defects
• It is absorbed by duodenum/proximal jejunum
• Causes of deficiency:
o Poor diet, eg poverty, alcoholics, elderly
o Increased demand, eg pregnancy or cell turnover (seen in haemolysis, malignancy,
inflammatory disease and renal dialysis)
o Malabsorption, eg coeliac disease, tropical sprue
o Drugs, alcohol, anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim.
• Treatment: Assess for an underlying cause, eg poor diet, malabsorption
o Treat with folic acid 5mg/day PO for 4 months, never without B12 as in low B12
states it may precipitate, or worsen, subacute combined degeneration of the cord
o In pregnancy prophylactic doses of folate (400μg/day) are given from conception
until at least 12wks; this helps prevent spina bifida, as well as anaemia.
o NB: if ill (eg CCF) with megaloblastic anaemia, it may be necessary to treat before
serum B12 and folate results are known
• Folate and ischaemic heart disease studies have indicated that higher homocysteine
concentrations are associated with a greater risk of coronary heart disease; folic acid
supplementation may have a role in prevention by lowering homocysteine.
• Folate and cognition ff borderline folate deficiency (as shown by raised
homocysteine) 800μg folic acid/d for 3yrs has been found to benefit cognition.
B12 deficiency and pernicious anaemia

• Vitamin B12 is found in meat, fish, and dairy products, but not in plants but body stores
are sufficient for 4yrs
• It is protein-bound and released during digestion then binds to intrinsic factor in the
stomach, and this complex is absorbed in the terminal ileum
• Causes of deficiency:
o Dietary (eg vegans)
o Malabsorption: stomach (lack of intrinsic factor): pernicious anaemia, post
gastrectomy; terminal ileum: ileal resection, Crohn’s disease, bacterial
overgrowth, tropical sprue, tapeworms (diphyllobothrium)
• Features:
o General: Symptoms of anaemia, ‘lemon tinge’ to skin due to combination of pallor (anaemia) and mild jaundice (due to
haemolysis), glossitis (beefy-red sore tongue), angular cheilosis
o Neuropsychiatric: Irritability, depression, psychosis, dementia
o Neurological: Paraesthesiae, peripheral neuropathy
o Also: Subacute combined degeneration of the spinal cord: Onset with peripheral neuropathy (combination of symmetrical
posterior (dorsal) column loss, causing sensory and LMN signs, and symmetrical corticospinal tract loss, causing motor and UMN
signs)
§ Joint-position and vibration sense are often affected first leading to ataxia, followed by stiffness and weakness if untreated
§ The classical triad is: Extensor plantars (UMN), Absent knee jerks (LMN), Absent ankle jerks (LMN)
§ It may present with falls at night-time, due to a combination of ataxia and reduced vision, which is also seen with low B12
Pernicious anaemia (PA) is caused by an autoimmune atrophic gastritis, leading to

achlorhydria and lack of gastric intrinsic factor secretion.
• Incidence 1:1000; higher incidence if blood group A
• Associations:
o Other autoimmune diseases: thyroid disease (~25%), vitiligo, Addison’s
disease, hypoparathyroidism
o Carcinoma of stomach is ~3-fold more common in pernicious anaemia
• Tests:
o Hb, MCV, WCC and platelets
o Serum B12
o Reticulocytes
o Hypersegmented polymorphs
o Megaloblasts in the marrow
o Specific tests for PA:
§ Parietal cell antibodies: found in 90% with PA, but also in 3–10% without
§ Intrinsic factor (IF) antibodies: specific for PA, but lower sensitivity
• Treatment:
o If due to malabsorption, injections are required - replenish stores with
hydroxocobalamin (B12) 1mg IM alternate days, eg for 2wks; Maintenance: 1mg
IM every 3 months for life (child’s dose: as for adult)
o If the cause is dietary, then oral B12 can be given after the initial acute course
o Initial improvement is heralded by a transient marked reticulocytosis and hence raised MCV, after 4–5 days
o Transfusion is best avoided, but PA with high output CCF may require exchange transfusion
• Prognosis: Supplementation usually improves peripheral neuropathy within the first 3–6 months, but has little effect on cord signs
Michael Grant
lOMoARcPSD|4927727

Haemolytic anaemia
• History: Family history, race, jaundice, dark urine, drugs, previous anaemia, travel.
• Examination: Jaundice, hepatosplenomegaly, gallstones (pigmented, due to ฀bilirubin
from haemolysis), leg ulcers (due to poor blood flow)
• Tests: FBC, reticulocytes, bilirubin, LDH, haptoglobin, urinary urobilinogen
o Thick and thin films for malaria screen if history of travel: polychromasia and
macrocytosis due to reticulocytes, or point to the diagnosis:
§ Hypochromic microcytic anaemia (thalassaemia)
§ Sickle cells (sickle-cell anaemia)
§ Schistocytes (microangiopathic haemolytic anaemia)
§ Abnormal cells in haematological malignancy
§ Spherocytes (hereditary spherocytosis or autoimmune haemolytic anaemia)
§ Elliptocytes (hereditary elliptocytosis)
§ Heinz bodies, ‘bite’ cells (glucose-6-phosphate dehydrogenase deficiency)
• An approach is first to confirm haemolysis and then find the cause — try to answer these 4
questions:
1 Is there increased red cell breakdown? 
o Anaemia with normal or abnormal MCV. 
o Bilirubin: unconjugated, from haem breakdown (pre-hepatic jaundice).
o Urinary urobilinogen (no urinary conjugated bilirubin). 
o Serum lactic dehydrogenase (LDH), as it is released from red cells.
2 Is there increased red cell production? 
o Reticulocytes, causing abnormal MCV (reticulocytes are large immature RBCS) and
polychromasia.
3 Is the haemolysis mainly extra- or intravascular? 
§ Extravascular haemolysis may lead to splenic hypertrophy and splenomegaly
§ Features of intravascular haemolysis are: 
o Free plasma haemoglobin: released from RBCS
o Methaemalbuminaemia: some free Hb is broken down in the circulation to
produce haem and globin; haem combines with albumin to make
methaemalbumin
o Plasma haptoglobin: mops up free plasma Hb, then removed by the liver.
o Haemoglobinuria: causes red-brown urine, in absence of red blood cells
o Haemosiderinuria: occurs when haptoglobin-binding capacity is exceeded,
causing free Hb to be filtered by the renal glomeruli, absorption of free Hb via the renal tubules and storage in the tubular
cells as haemosiderin. This is detected in the urine in sloughed tubular cells by Prussian blue staining ~1 week after onset
(implying a chronic intravascular haemolysis)  
4 Why is there haemolysis? Causes:
Causes of haemolytic anaemia are divided into acquired—these are divided into immune
and non-immune causes.
• Immune-mediated and direct antiglobulin test +ve (Coombs test):
o Drug-induced Causing formation of RBC autoantibodies from binding to RBC
membranes (eg penicillin) or production of immune complexes (eg quinine)
o Autoimmune haemolytic anaemia (AIHA): Mediated by autoantibodies causing
mainly extravascular haemolysis and spherocytosis. Classify according to optimal
binding temperature to RBCs:
§ Warm AIHA: IgG-mediated, bind at body T° 37°C
• Treatment: Steroids/immunosuppressants (± splenectomy)
§ Cold AIHA: IgM-mediated, bind at low T° (<4°C), activating cell-surface
complement. Causes a chronic anaemia made worse by cold, often with
Raynaud’s or acrocyanosis.
• Treatment: Keep warm. Chlorambucil may help
• Causes: Most are idiopathic; 2° causes of warm AIHA include
lymphoproliferative disease (CLL, lymphoma), drugs, autoimmune
disease, eg SLE. Cold AIHA may follow infection (mycoplasma; EBV)
o Paroxysmal cold haemoglobinuria is seen with viruses/syphilis. It is caused by
Donath–Landsteiner antibodies sticking to RBCS in the cold, causing self- limiting
complement-mediated haemolysis on rewarming. Isoimmune: Acute transfusion
reaction (p359); haemolytic disease of newborn
• Direct antiglobulin/Coombs –ve AIHA: (2% of all AIHA) Autoimmune hepatitis;
hepatitis B & C; post flu and other vaccinations; drugs (piperacillin, rituximab)
• Microangiopathic haemolytic anaemia (MAHA): A mechanical disruption of RBCS in
circulation, causing intravascular haemolysis and schistocytes
o Causes include haemolyticuraemic syndrome (HUS), TTP, DIC, pre-eclampsia
• Infection: Malaria: RBC lysis and ‘blackwater fever’ (haemoglobinuria)
• Paroxysmal nocturnal haemoglobinuria (Marchiafava–Micheli disease) is a rare
acquired stem cell disorder, with haemolysis (esp. at night), marrow failure +
Michael Grant
lOMoARcPSD|4927727

thrombophilia. Visceral thrombosis (hepatic, mesenteric, renal and CNS veins) and pulmonary emboli predict poor outcome
§ Ham’s test +ve (in vitro acid-induced lysis, rarely done)
§ Treatment: Anticoagulation. Eculizumab has a role, so stem cell transplantation is less needed.
• Hereditary
o Enzyme defects:
§ Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the chief RBC enzyme defect but most are asymptomatic, but may
get oxidative crises due to low glutathione production, precipitated by drugs (eg primaquine, sulfonamides, aspirin), exposure
to Vicia fava (broad beans/favism), or illness
• In attacks, there is rapid anaemia and jaundice
• Film: bite- and blister-cells
• Treatment: Avoid precipitants (eg, henna, fig 8); transfuse if severe
§ Pyruvate kinase deficiency decreased ATP production causes decreases RBC survival. Homozygotes have neonatal jaundice;
later, haemolysis with splenomegaly ± jaundice
• Treatment: Often not needed; splenectomy may help
o Membrane defects: All are Coombs –ve; all need folate; splenectomy helps some
§ Hereditary spherocytosis Prevalence: 1:3000. Less deformable spherical RBCS, so trapped in spleen causing extravascular
haemolysis. Signs: Splenomegaly, jaundice, raised Bilirubin (risk of gallstones)
§ Hereditary elliptocytosis dominant; Mostly asymptomatic (somewhat protects from malaria). 10% display a more severe
phenotype (± death in utero)
§ Hereditary ovalocytosis and stomatocytosis are rarer. Refer to a haematologist
o Haemoglobinopathy: • Sickle-cell disease (Hydroxycarbamide if frequent crises) • Thalassaemia
Bleeding disorders
After injury, 3 processes halt bleeding: vasoconstriction, gap-plugging by platelets, and the
coagulation cascade:
o Vascular and platelet disorders lead to prolonged bleeding from cuts, bleeding
into the skin (eg easy bruising and purpura), bleeding from mucous membranes (eg
epistaxis, bleeding from gums, menorrhagia)
o Coagulation disorders cause delayed bleeding into joints and muscle
• Vascular defects
o Congenital: Osler–Weber–Rendu syndrome, connective tissue disease (eg Ehlers–
Danlos syndrome, pseudoxanthoma elasticum)
o Acquired: Senile purpura, infection (eg meningococcal, measles, dengue fever),
steroids, scurvy (perifollicular haemorrhages), Henoch–Schönlein purpura, painful
bruising syndrome—women who develop tingling under the skin followed by bruising
• Platelet disorders
o Decreased marrow production: Aplastic anaemia, megaloblastic anaemia, marrow infiltration (eg
leukaemia, myeloma), marrow suppression (cytotoxic drugs, radiotherapy)
o Excess destruction:
§ Immune: Immune thrombocytopenic purpura (ITP), other autoimmune causes, eg SLE, CLL,
drugs, eg heparin, viruses
§ Non-immune: DIC, thrombotic thrombocytopenic purpura (TTP) or HUS, sequestration (in
hypersplenism)
§ ITP is caused by antiplatelet autoantibodies. It is acute (usually in children, 2wks after infection
with sudden self-limiting purpura) or chronic (seen mainly in women - runs a fluctuating course
of bleeding, purpura (esp. dependent pressure areas), epistaxis and menorrhagia and there is
no splenomegaly)
• Tests in ITP: high megakaryocytes in marrow, antiplatelet autoantibodies often present.
• Treatment: None if mild. If symptomatic or platelets <20 ≈ 109/L, prednisolone 1mg/kg/d
o If relapse, splenectomy cures ≤80%
o If this fails: immunosuppression, eg azathioprine or cyclophosphamide
o IV immunoglobulin may temporarily raise the platelet count, eg for surgery, pregnancy
o Eltrombopag is a new oral thrombopoietin-receptor agonist that stimulates
thrombopoiesis
• Coagulation disorders
o Congenital: Haemophilia, von Willebrand’s disease
§ Haemophilia A – Factor VIII deficiency; inherited in an X-linked recessive pattern in 1:10,000
male births—usually due to a ‘flip tip’ inversion in the factor VIII gene in the X chromosome
• Presentation depends on severity and is often early in life or after surgery/ trauma—with bleeds into joints leading to
crippling arthropathy, and into muscles causing haematomas (with pressure can lead to nerve palsies and
compartment syndrome)
• Diagnose by ฀APTT and ฀factor VIII assay. Management: Seek expert advice. Avoid NSAIDS and IM injections (fig 2).
Minor bleeding: pressure and elevation of the part. Desmopressin (0.3μg/kg/12h IVI over 20min) raises factor VIII levels,
and may be su cient. Major bleeds (eg haemarthrosis): ฀factor VIII levels to 50% of normal. Life-threatening bleeds (eg
obstructing airway) need levels of 100%, eg with recombinant factor VIII. Genetic counselling
§ Haemophilia B – (Christmas disease) Factor IX deficiency (inherited, X-linked recessive); behaves clinically like haemophilia A
o Acquired: Anticoagulants, liver disease, DIC, vitamin K deficiency.
Michael Grant
lOMoARcPSD|4927727
Acquired haemophilia is a bleeding diathesis causing big mucosal

bleeds in males and females caused by suddenly appearing
autoantibodies that interfere with factor VIII.
• Tests: raised APPT; VIII autoantibody; factor VIII activity <50%
• Treatment: Steroids.
Liver disease produces a complicated bleeding disorder with synthesis

of clotting factors, decreased absorption of vitamin K, and
abnormalities of platelet function.
Malabsorption leads to less uptake of vitamin K (needed for synthesis

of factors II, VII, IX, and X). Treatment is IV vitamin K (10mg) or FFP for
acute haemorrhage.
In cases of bleeding disorders, what is the mechanism? To help find

the answer do FBC, film, and coagulation tests (citrate tube; false results
if under-filled):
• Prothrombin time (PT): Thromboplastin is added to test the
extrinsic system
o PT is expressed as a ratio compared to control [International
Normalized Ratio (INR), normal range = 0.9–1.2]. It tests for
abnormalities in factors I, II, V, VII, X.
o Prolonged by: warfarin, Vit K deficiency, liver disease, DIC
• Activated partial thromboplastin time (APTT): Kaolin is added to
test the intrinsic system. Tests for abnormalities in factor I, II, V, VIII,
IX, X, XI, XII
o Normal range 35–45s
o Prolonged by: heparin, haemophilia, DIC, liver disease.
• Thrombin time: Thrombin is added to plasma to convert fibrinogen
to fibrin. Normal range: 10–15s
o Prolonged by: heparin treatment, DIC, dysfibrinogenaemia.
• D-dimers are a fibrin degradation product, released from cross-
linked fibrin during fibrinolysis. This occurs during DIC, or in the presence of venous
thromboembolism—deep vein thrombosis (DVT) or pulmonary embolism (PE)
o D-dimers may also be raised in inflammation, eg with infection or malignancy.
• Bleeding time tests haemostasis – It is done by making two small incisions into the
skin of the forearm.
Normal time to haemostasis: 10min.51
NB: this is rarely done, as it is operator dependent; consider the PFA-100
Anticoagulants can be used for:

o Therapeutic: Venous thromboembolic disease: DVT and PE.
o Prophylactic: Prevention of DVT/PE in high-risk patients, eg post-op.,
Prevention of stroke, eg in chronic AF or prosthetic heart valve
• Heparin
o Low molecular weight heparin (LMWH) Given s.c. - eg dalteparin,
enoxaparin, tinzaparin
§ Inactivates factor Xa (but not thrombin)
§ T1⁄2 is 2- to 4-fold longer than standard heparin; response more
predictable
§ Accumulates in renal failure: lower for prophylaxis, or UFH for
therapeutic
• Unfractionated heparin (UFH) IV or SC
o A glycosaminoglycan, which binds antithrombin (an endogenous inhibitor of
coagulation), increasing its ability to inhibit thrombin, factor Xa, and IXa
o Rapid onset and has a short T1⁄2
o Monitor and adjust dose with APTT
• SE for both: Bleeding (eg at operative site, gastrointestinal, intracranial), heparin-
induced thrombocytopenia (HIT), osteoporosis with long-term use.
o HIT and osteoporosis are less common with LMWH than UFH. Beware
hyperkalaemia
• CI: Bleeding disorders, platelets <60≈109/L, previous HIT, peptic ulcer, cerebral
haemorrhage, severe hypertension, neurosurgery
• Warfarin is used orally once daily as long-term anticoagulation. The therapeutic
range is narrow, varying with the condition being treated and is measured as a ratio
compared with the standard INR
o Warfarin inhibits the reductase enzyme responsible for active form of vitamin K
Michael Grant
lOMoARcPSD|4927727

o CI: Peptic ulcer, bleeding disorders, severe hypertension, pregnancy (teratogenic)
o Use with caution in the elderly and those with past GI bleeds. In the UK, warfarin tablets are 0.5mg (white), 1mg (brown), 3mg (blue),
or 5mg (pink)
• Others:
o Fondaparinux is a pentasaccharide Xa inhibitor and may be used in place of LMWH for prophylaxis in certain situations.
o Factor Xa inhibitors (rivaroxaban and apixaban) and direct thrombin inhibitors (dabigatran) are new oral anticoagulants that do
not need monitoring—but they have not yet displaced warfarin.
• Beginning therapeutic anticoagulation (follow local guidelines, and see BNF) for
treatment of venous thromboembolism, LMWH or UFH are used initially, and
warfarin is given in combination usually from day 1. Heparin should be continued
until INR has reached target therapeutic range and until day 5, as warfarin has an
initial prothrombotic effect
o LMWH Dose according to weight – typcailly 1.5mg/kg/24hr
o UFH IV infusion: Give heparin 5000iu IV bolus over 30min (10,000iu in severe
PE)
§ Prepare syringe pump: with 0.9% saline
§ Infuse heparin at a rate of 18 units/kg/h. Check APTT at 6h, aim for APTT
ratio
§ Measure APTT daily or 10h after dose change
o Warfarin is given daily; start with 10mg stat at 18.00. Do INR 16h later.
§ If INR <1.8 (as is likely) the 2nd dose of warfarin is 5 or 10mg at 18.00
(24h after first dose)
• Give the lower dose if >60yrs, liver disease, or cardiac failure
• But if INR >1.8 (warfarin sensitivity; rare) give just 0.5mg
§ Do INR daily for 5d and adjust dose
§ Stop heparin after 5d and when INR >2 for 2d. Tell lab when stopped.
§ Measure INR on alternate days until stable, then weekly or less often.
• Antidotes
o If UFH overdose: stop infusion. If there is bleeding, protamine sulfate
counteracts UFH: discuss with a haematologist
o Warfarin: See box to right
Lymphomas are disorders caused by malignant proliferations of lymphocytes. These

accumulate in the lymph nodes causing lymphadenopathy, but may also be found in
peripheral blood or infiltrate organs. Lymphomas are histologically divided into Hodg
kin’s and non-Hodgkin’s types.
• Hodgkin’s lymphoma (HL) characteristic cells with mirror-image nuclei are found,
called Reed–Sternberg cells
o Incidence 2 peaks of incidence: young adults and elderly.
o Increased risk if: an affected sibling; EBV; SLE; post-transplantation;
westernization; obese.
o Symptoms:
§ Enlarged, painless, non-tender, ‘rubbery’ superficial lymph nodes,
typically cervical (60–70%), also axillary or inguinal nodes
§ 25% have constitutional upset, eg fever, weight loss, night sweats, lethargy.
§ There may be alcohol-induced lymph node pain
§ Mediastinal lymph node involvement can cause features due to mass
effect, eg bronchial or SVC obstruction
§ Pel–Ebstein fever implies a cyclical fever with long
periods (15–28 days) of normal or low temperature
o Signs: Lymph node enlargement; Also, cachexia, anaemia,
spleno- or hepatomegaly
o Tests: Lymph node excision biopsy if possible
§ Image-guided needle biopsy, laparotomy or
mediastinoscopy may be needed to obtain a sample.
§ Bloods FBC, film, ESR, LFT, LDH (raised as it is released
during cell turnover), urate, Ca2+
o Staging (Ann Arbor system) Influences treatment and prognosis. Done by CXR, CT/PET of
thorax, abdo, pelvis ± marrow biopsy if B symptoms, or stage III–IV disease:
I Confined to single lymph node region.
II Involvement of two or more nodal areas on the same side of the diaphragm.
III Involvement of nodes on both sides of the diaphragm.
IV Spread beyond the lymph nodes, eg liver or bone marrow
§ Each stage is either ‘A’— no systemic symptoms other than pruritus; or ‘B’—presence of B
symptoms:
• Weight loss >10% in last 6 months, unexplained fever >38°C, or night sweats (needing
change of clothes). ‘B’ indicates worse disease.
Michael Grant
lOMoARcPSD|4927727

o Chemoradiotherapy: Radiotherapy ± short courses of chemotherapy for stages I-A and II-A (eg with ≤3 areas involved). Longer
courses of chemotherapy for II-A with >3 areas involved through to IV-B.
§ ‘ABVD’: Adriamycin, Bleomycin, Vinblastine, Dacarbazine (+ radiotherapy in younger patients) cures ~80% of patients.
§ In relapsed disease, high-dose chemotherapy with peripheral stem-cell transplants may be used, involving autologous (or
occasionally allogeneic) transplantation of peripheral blood progenitor cells to restore marrow function after therapy.
Non-Hodgkin’s lymphoma includes all lymphomas without Reed–Sternberg cells—a diverse group.
• Most are derived from B-cell lines; diffuse large B-cell lymphoma (DLBCL) is commonest.
• Not all centre on nodes (extranodal tissues generating lymphoma include mucosa-associated lymphoid tissue, eg gastric MALT).
• Causes: Immunodeficiency—drugs; HIV (usually high-grade lymphoma from EBV transformed cells); HTLV-1; H. pylori ; toxins; congenital
• The patient:
o Nodal disease (75% at presentation): superficial lymphadenopathy
o Extranodal disease (25%):
§ Skin: T-cell lymphomas: Sézary syndrome (p598 & fig 1)
§ Oropharynx: Waldeyer’s ring lymphoma causes sore
throat/obstructed breathing
§ Gut:
• Gastric MALT is caused by H. pylori, and may regress with
its eradication; Symptoms: like gastric Ca, with systemic features (fever, sweats). MALT usually involves the antrum, is
multifocal, and metastasizes late
• Non-MALT gastric lymphomas (60%) are usually diffuse large-cell B lymphomas—high-grade and not responding well to H.
pylori eradication
• Small-bowel lymphomas are IPSID (immunoproliferative small intestine disease), MALT or enteropathy/coeliac-associated
intra-epithelial T-cell lymphoma— presents with diarrhoea, vomiting, abdominal pain, and weight. Poor prognosis.
• Systemic symptoms—fever, night sweats, weight loss (less common than in Hodgkin’s lymphoma, and indicates disseminated disease).
• Pancytopenia from marrow involvement—anaemia, infection, bleeding (low platelets)
• Tests Blood: FBC, U&E, LFT.
o LDH ≈ worse prognosis, reflecting high cell turnover. Marrow and node biopsy for classification (a complex, changing quagmire,
based on the WHO system of high- or low-grade)
o Staging Ann Arbor system —CT/MRI of chest, abdomen, pelvis
o Send cytology of any effusion; LP for CSF cytology if CNS signs.
• Diagnosis/management is multidisciplinary, synthesizing details from clinical evaluation, histology, immunology, molecular genetics, and
imaging. Generally:
o Low-grade lymphomas are indolent, often incurable and widely disseminated. Include: follicular lymphoma, marginal zone
lymphoma/MALT, lymphocytic lymphoma, lymphoplasmacytoid lymphoma (produces IgM = Waldenström’s macroglobulinaemia)
o High-grade lymphomas are more aggressive, but often curable. There is often rapidly enlarging lymphadenopathy with systemic
symptoms. Include: Burkitt’s lymphoma (childhood disease with characteristic jaw lymphadenopathy), lymphoblastic lymphomas (like
ALL), diffuse large B-cell lymphoma.
• Treatment Depends on disease subtype:
o Low grade: If symptomless, none may be needed. Radiotherapy may be
curative in localized disease. Chlorambucil is used in diffuse disease.
Remission may be maintained by using interferon or rituximab (anti-
CD20 is widely expressed on B cells, from early pre-B cells to later in
differentiation, but it is absent on fully differentiated plasma cells).
o High grade: (eg large B-cell lymphoma, DLBCL), ‘R-CHOP’ regimen:
Rituximab Cyclophosphamide, Hydroxydaunorubicin, vincristine
(Oncovin®) and Prednisolone.
§ Granulocyte colony-stimulating factors (G-CSFs) help neutropenia
— eg filgrastim or lenograstim
Leukaemias patients (esp. AML) fall ill suddenly and deteriorate fast, eg with:
Infection, Bleeding (Rx: platelets ± FFP) and hyperviscosity.
• Have low threshold to investigate: do blood cultures, glucose U&E, LFT,
Ca2+ and clotting.
• Neutropenic regimen (for when neutrophil count ≤0.5 ≈ 109/L):
o Abide by infection control procedures! Use a risk-assessment
tool (eg MASCC)
o Full barrier nursing if possible. Hand-washing is vital. Use a side
room.
o Avoid IM injections (danger of an infected haematoma)
o Check: FBC, platelets, INR, U&E, LFT, LDH, CRP. Take cultures
(blood ≈ 3—peripherally± Hickman line; urine, sputum, stool if
diarrhoea)•Wash perineum after defecation
o Vases containing cut flowers pose a Pseudomonas risk
o If T° >38°C or T° >37.5°C on 2 occasions, >1h apart, or the
patient is toxic, assume septicaemia and start blind
combination therapy—eg piperacillin–tazobactam
Michael Grant
lOMoARcPSD|4927727

o Consider treatment for Pneumocystis (eg
co-trimoxazole, ie trimethoprim 20mg/kg
+ sulfamethoxazole 100mg/kg/day PO/IV
in 2 daily doses)
o Tumour lysis syndrome: Caused by a
massive destruction of cells leading to
K+ increase, urate and renal injury.
§ Prevention: high fluid
intake+allopurinol pre-cytotoxics.
For those at high risk of cell lysis,
recombinant uricase (rasburicase)
may be given
o Hyperviscosity: If WCC is >100≈109/L
WBC thrombi may form in brain, lung,
and heart (leukostasis)
o DIC: Consumptive coagulopathy, from
release of procoagulants into the
circulation with consumption of clotting factors and platelets, fibrin strands fill small
vessels, haemolysing passing RBCs.
§ Causes: Malignancy, sepsis, trauma, obstetric events
§ Signs: Bruising, bleeding anywhere (eg venepuncture sites), renal failure.
§ Tests: Platelets฀; PT฀; APTT฀; fibrinogen฀ (correlates with severity); fibrin
degradation products (D-dimers)
§ Film: broken RBCS (schistocytes)
§ Rx: Treat the cause. Replace platelets if <50≈109/L, cryoprecipitate to replace
fibrinogen, FFP to replace coagulation factors
§ The use of alltransretinoic acid (ATRA) has significantly reduced the risk of DIC in
acute promyelocytic leukaemia (the commonest leukaemia associated with DIC).
o Preventing sepsis: Fluoroquinolone (eg ciprofloxacin) before neutropenia gets serious;
granulocyte colony stimulators are of limited use. Herpes, pneumocystis and CMV
(valganciclovir) prophylaxis have a role
Acute lymphoblastic leukaemia (ALL) is a malignancy of lymphoid

cells, affecting B or T lymphocyte cell lines, arresting maturation
and promoting uncontrolled proliferation of immature blast cells,
with marrow failure and tissue infiltration.
• It is thought to develop from a combination of genetic
susceptibility (eg with translocations, and gains and losses of
whole chromosomes) + an environmental trigger
o Ionizing radiation, eg X-rays, during pregnancy, and Down’s
syndrome are important associations
• It is the commonest cancer of childhood, and is rare in adults
• Classification is based on 3 systems:
o Morphological The FAB system (French, American, British)
divides ALL into 3 types (L1, L2, L3) by microscopic appearance. Provides limited information
o Immunological Surface markers are used to classify ALL into:
§ Precursor B-cell ALL
§ T-cell ALL
§ B-cell ALL
o Cytogenetic Chromosomal analysis. Abnormalities are detected in up to 85%, which are often translocations. Useful for predicting
prognosis, eg poor with Philadelphia (Ph) chromosome and for detecting disease recurrence
• Signs and symptoms are due to:
o Marrow failure: Anaemia (฀Hb), infection (฀WCC), and bleeding (฀platelets)
o Infiltration: Hepato- and splenomegaly, lymphadenopathy—superficial or mediastinal, orchidomegaly, CNS involvement—eg
cranial nerve palsies, meningism
o Common infections: Especially chest, mouth, perianal and skin. Bacterial septicaemia, zoster, CMV, measles, candidiasis,
Pneumocystis pneumonia
• Tests: Characteristic blast cells on blood film and bone marrow
o WCC usually high
o CXR and CT scan to look for mediastinal and abdominal lymphadenopathy
o Lumbar puncture should be performed to look for CNS involvement.
• Support: Blood/platelet transfusion, IV fluids, allopurinol (prevents tumour lysis syndrome)
o Insert a subcutaneous port system/Hickman line for IV access
o Infections: Immediate IV antibiotics for infection. Start the neutropenic regimen: prophylactic antivirals, antifungals and antibiotics•
o Chemotherapy: A typical programme is: Remission induction: eg vincristine, prednisolone, L-asparaginase + daunorubicin.
o CNS prophylaxis: Intrathecal (or high-dose IV) methotrexate ± CNS irradiation
• Relapse is common in blood, CNS, or testis (examine these sites at follow-up)
• Matched related allogeneic marrow transplantations once in 1st remission is the best option in standard-risk younger adults (?too
many SE if older)
Michael Grant
lOMoARcPSD|4927727

• Prognosis: Cure rates for children are 70–90%; for adults only 40% (higher when imatinib [specific BCR-ABL tyrosine kinase inhibitor]
/rituximab)
• Poor prognosis if: adult, male, Philadelphia chromosome:
o BCR–ABL gene fusion due to translocation of chromosomes 9 and 22 or B-cell ALL
Acute myeloid leukaemia (AML) is a neoplastic proliferation of blast cells is derived from marrow myeloid elements. It progresses rapidly
(death in ~2 months if untreated; ~20% 3yr survival after Rx)
• Incidence: The commonest acute leukaemia of adults (1/10,000/yr)
• AML can be a long-term complication of chemotherapy, eg for lymphoma
• Also associated with myelodysplastic states, radiation, and syndromes, eg
Down’s
• 5 types:
o 1 AML with recurrent genetic abnormalities.
o 2 AML multilineage dysplasia (eg 2° to pre-existing myelodysplastic
syndrome).
o 3 AML, therapy related.
o 4 AML, other.
o 5 Acute leukaemias of ambiguous lineage (both myeloid and lymphoid
phenotype)
• Symptoms:
o Marrow failure: Symptoms of anaemia, infection or bleeding
o DIC occurs in acute promyelocytic leukaemia, a subtype of AML,
where there is release of thromboplastin. Use of all-transretinoic acid
with chemotherapy reduceds risk of DIC
o Infiltration: Hepatomegaly and splenomegaly, gum hypertrophy (fig
3), skin involvement
• Diagnosis: WCC is often raised, but can be normal or even low
o Blast cells may be few in the peripheral blood, so diagnosis depends on bone marrow biopsy.
o Differentiation from ALL may be by microscopy (Auer rods are diagnostic of AML), but is now based on immunophenotyping and
molecular methods
o Cytogenetic analysis (eg type of mutation) affects treatment recommendations, and guides prognosis
• Complications: Infection is the major problem, related to both the disease and during treatment
o Pitfalls: AML itself causes fever, common organisms present oddly, few antibodies are made, rare or-anisms—particularly fungi (esp.
Candida or Aspergillus)
o Chemotherapy causes: plasma urate levels (from tumour lysis)—so give allopurinol with chemotherapy, and keep well hydrated
with IV fluids
o Leukostasis may occur if WCC raised
• Treatment: Supportive care As for ALL. Walking exercises can relieve fatigue.
o Chemotherapy is very intensive, resulting in long periods of marrow suppression with neutropenia + platelets
o The main drugs used include daunorubicin and cytarabine, with ~5 cycles given in 1-week blocks to get a remission (RAS mutations
occur in ~20% of patients with AML and enhance sensitivity to cytarabine)
o Bone marrow transplant (BMT) Pluripotent haematopoietic stem cells are collected from the marrow and allogeneic transplants from
HLA-matched siblings or matched unrelated donors (held on international databases) are indicated during 1st remission in
disease with poor prognosis.
§ The idea is to destroy leukaemic cells and the immune system by cyclophosphamide + total body irradiation, and then
repopulate the marrow by transplantation from a matched donor infused IV
§ BMT allows the most intensive chemotherapy regimens because marrow suppression is not an issue
§ Ciclosporin ± methotrexate are used to reduce the effect of the new marrow attacking the patient’s body (graft vs host
disease)
§ Complications: Graft vs host disease (may help explain the curative effect of BMT); opportunistic infections; relapse of leukaemia;
infertility.
• Prognosis: Lower relapse rates ~60% long-term survivors, but significant mortality of
~10%. Autologous BMT where stem cells are taken from the patient themselves, is
used in intermediate prognosis disease, although some studies suggest better
survival rates with intensive chemotherapy regimens.
• Autologous mobilized peripheral blood stem cell transplantation may offer faster
haemopoietic recovery and less morbidity
• Supportive care, or lower-dose chemotherapy for disease control, may be more
appropriate in elderly patients, where intensive therapies have poorer outcomes.
Chronic myeloid leukaemia (CML) is characterized by an uncontrolled clonal

proliferation of myeloid cells (fig 1)
• Accounts for 15% of leukaemias. It is a myeloproliferative disorder having features in
common with these diseases, eg splenomegaly
• It occurs most often between 40–60yrs, with a slight male predominance, and is rare
in childhood
• Philadelphia chromosome (Ph) Present in >80% of those with CML - is a hybrid
chromosome comprising reciprocal translocation between the long arm of
Michael Grant
lOMoARcPSD|4927727

chromosome 9 and the long arm of chromosome 22—t(9;22)—forming a fusion gene
BCR/ ABL on chromosome 22, which has tyrosine kinase activity.
o Those without Ph have a worse prognosis
o Some patients have a masked translocation—cytogenetics do not show the Ph, but
the rearrangement is detectable by molecular techniques
• Symptoms:
o Mostly chronic and insidious: weight loss, tiredness, fever, sweats
o There may be features of gout (due to purine breakdown), bleeding (platelet
dysfunction), and abdominal discomfort (splenic enlargement)~30% are detected by
chance
• Signs Splenomegaly (>75%)—often massive. Hepatomegaly, anaemia, bruising
• Tests WBC (often >100≈109/L) with whole spectrum of myeloid cells, ie. neutrophils,
myelocytes, basophils, eosinophils. Hb low or normal, platelets variable. Urate, B12.
o Bone marrow is hypercellular
o Ph found on cytogenetic analysis of blood or bone marrow
• Natural history Variable, median survival 5–6yrs
o There are 3 phases:
o Chronic, lasting months or years of few, if any, symptoms ฀
o Accelerated phase, with increasing symptoms, spleen size, and di culty in
controlling counts ฀
o Blast transformation, with features of acute leukaemia ± death. Treatment See
BOX.
Chronic lymphocytic leukaemia (CLL) is an accumulation of mature B cells that have

escaped programmed cell death and undergone cell-cycle arrest in the G0/G1 phase is
the hallmark of CLL
• It is the commonest leukaemia (>25%; incidence:
~4/100,000/yr)
• Symptoms Often none, presenting as a surprise finding on a
routine FBC (eg done pre-op)
o May be anaemic or infection-prone
o If severe: weight loss, sweats, anorexia
• Signs: Enlarged, rubbery, non-tender nodes. Splenomegaly, hepatomegaly
• Tests: Lymphocytes—may be marked
o Later: autoimmune haemolysis, marrow infiltration
• Complications:
o 1 Autoimmune haemolysis
o 2 Infection due to hypogammaglobulinaemia (=฀IgG), bacterial, viral
especially herpes zoster
o 3 Marrow failure
• Natural history usually nodes slowly enlarge (± lymphatic obstruction);
o Death is often due to infection (commonly pneumococcus, haemophilus,
meningococcus, Candida or aspergillosis), or transformation to
aggressive lymphoma Richter’s syndrome
o Richter’s syndrome - 5-10% of B cell chronic lymphocytic leukemia (CLL)
and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma,
a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis)
• Treatment
o Consider drugs if: Symptomatic, Immunoglobulin genes (IgVH) are unmutated,17p deletions (consider intensive Rx)
o Fludarabine + cyclophosphamide + rituximab is 1st line (there is synergism)
o Steroids help autoimmune haemolysis
o Radiotherapy helps treat lymphadenopathy and splenomegaly. Supportive care:
Transfusions, IV human immunoglobulin if recurrent infection
o Relapsed disease: One option is rituximab + dexamethasone (R-DEX)
o Prognosis 1⁄3 never progress, 1⁄3 progress slowly, and 1⁄3 progress actively.
CD23 and microglobulin correlate with bulk of disease and rates of progression.
Multiple myeloma is the chief plasma cell dyscrasia. These are due to an abnormal
proliferation of a single clone of plasma or lymphoplasmacytic cells leading to
secretion of immunoglobulin (Ig) or an Ig fragment, causing the dysfunction of many
organs (esp kidney)
• The Ig is seen as a monoclonal band, or paraprotein, on serum or urine
electrophoresis (see below)
• Classification is based on immunoglobulin (Ig) product— IgG in ~2⁄3; IgA in ~1⁄3
• A very few are IgM or IgD
o Other Ig levels are low (‘immunoparesis’, causing susceptibility to infection)
o In ~ 2⁄3, urine contains Bence Jones proteins, which are free Ig light chains of
kappa (κ) or lambda (λ) type, filtered by the kidney
Michael Grant
lOMoARcPSD|4927727

o Do serum protein electrophoresis & ESR on all over 50 with back pain
o Osteolytic bone lesions causing backache, pathological fractures (eg long
bones or ribs) and vertebral collapse - Lesions are due to osteoclast
activation, from signalling by myeloma cells
o Hypercalcaemia may be symptomatic
• Anaemia, neutropenia, or thrombocytopenia may result from marrow
infiltration by plasma cells, leading to symptoms of anaemia, infection and
bleeding.
• Recurrent bacterial infections due to immunoparesis, and also because of
neutropenia due to the disease and from chemotherapy
• Renal impairment due to light chain seen in up to 20% at diagnosis — mainly
caused by precipitation of light chains with the Tamm-Hors-fall protein in the
distal loop of Henle.
o A rare type of damage is deposits of light chains in the form of AL-amyloid
(primary) and subsequent nephrosis
• Tests:
o FBC — normocytic normochromic anaemia
o Film — rouleaux formation, persistently raised ESR or plasma viscosity),
urea and creatinine, raised Ca2+ (in ~40%), alk phos usually raised unless
healing fracture
o Screening test: Serum and urine electrophoresis
o Imaging: X-rays: lytic ‘punched-out’ lesions, eg pepper-pot skull,
vertebral collapse, fractures or osteoporosis.
§ CT or MRI may be useful to detect lesions not seen on XR
o Treatment:
§ Supportive: Bone pain should be treated with analgesia (avoid
NSAIDS due to risk of renal impairment)
§ Give all patients a bisphosphonate (pamidronate), as they reduce
fracture rates and bone pain
§ Local radiotherapy can help rapidly in focal disease
§ Orthopaedic procedures (vertebroplasty or kyphoplasty – bone
cement injected into cracks) may be helpful in vertebral collapse.
§ Anaemia should be corrected with transfusion, and erythropoietin
may be used.
§ Renal failure: rehydrate, and ensure adequate fluid intake of 3L/day
to prevent further renal impairment by light chains.
§ Infections: Treat rapidly with broad-spectrum antibiotics until culture
results are known
• Regular IV immunoglobulin infusions may be needed if recurrent
§ Chemotherapy: If unsuitable for intensive, melphalan + prednisolone is
used. This can control disease for ~1yr, reducing paraprotein levels and
bone lesions. Adding bortezomib increases the time to relapse. In due
course, disease may become uncontrollable and resist treatment.
Adding thalidomide (a teratogenic immunomodulator) improves
event-free survival
• SE: birth defects; drowsiness; neuropathy; neutropenia; sepsis;
orthostatic hypotension; thromboembolism (aspirin, or full
anticoagulation)
§ In fitter people, a more vigorous approach is used (high-dose therapy
and stem-cell rescue, HDT) with a VAD type regimen: Vincristine, Adriamycin and Dexamethasone.
• Allogeneic transplantation can be curative in younger patients, but carries increased risk of mortality (~30%)
o Prognosis Worse if: >2 osteolytic lesions; Cause of death: infection; renal failure (transplants have a role
Polycythaemia may be relative (decreased plasma volume, normal RBC mass) or

absolute (increased RBC mass)
• Relative polycythaemia may be acute and due to dehydration (eg alcohol or
diuretics)
o A more chronic form exists which is associated with obesity, hypertension, and a high alcohol and
tobacco intake
• Absolute polycythaemia is distinguished by red cell mass estimation using radioactive chromium
(51Cr) labelled RBCs
o Causes are:
§ Primary - Polycythaemia rubra vera
• A Polycythaemia rubra vera This is a malignant proliferation of a clone derived from
one pluripotent marrow stem cell. A mutation in JAK2 (JAK2 V617F) is present in
>90%. The erythroid progenitor offspring are unusual in not needing erythropoietin
to avoid apoptosis (p511). There is excess proliferation of RBCs, WBCs, and platelets,
leading to hyperviscosity and thrombosis. Commoner if >60yrs old
• Signs:
Michael Grant
lOMoARcPSD|4927727

o May be asymptomatic or vague signs due to hyperviscosity: headaches,
dizziness, tinnitus, visual disturbance, gout (from RBC turnover)
o Itch after a hot bath, and erythromelalgia (a burning sensation in fingers
and toes - rare vascular peripheral pain disorder in which blood vessels are
episodically blocked, then become hyperemic and inflamed)
o Examination may show facial plethora and splenomegaly (in 60%)
o Investigations:
§ FBC: RCC, Hb, HCT, PCV, often also WBC and platelets
§ B12
§ Marrow shows hypercellularity with erythroid hyperplasia
§ Serum erythropoietin
§ Raised red cell mass on 51Cr studies and splenomegaly, in the
setting of a normal PaO2, is diagnostic.
o Treatment: Aim to keep HCT <0.45 to reduce risk of thrombosis
§ In younger patients at low risk, this is done by venesection
§ If higher risk (age >60yrs, previous thrombosis), hydroxycarbamide
(=hydroxyurea; used in sickle cell) is used
o Prognosis: Variable, many remain well for years. Thrombosis and
haemorrhage (due to defective platelets) are the main complications.
Transition to myelofibrosis (proliferation of an abnormal clone of
hematopoietic stem cells in the bone marrow and other sites results in
fibrosis) occurs in ~30% or acute leukaemia in ~5%.
§ Secondary: due to hypoxia (eg high altitudes, chronic lung disease, cyanotic congenital heart disease, heavy smoking) or
inappropriately raised erythropoietin secretion (eg in renal carcinoma, hepatocellular carcinoma).
Essential thrombocythaemia is a clonal proliferation of megakaryocytes leads to

persistently raisedplatelets, often >1000≈109/L, with abnormal function, causing bleeding or
arterial and venous thrombosis, and microvascular occlusion — seen as headache, atypical
chest pain, light-headedness, erythromelalgia
• Exclude other causes of thrombocytosis (see BOX)
• Treatment: Low-dose aspirin 75mg daily
o Hydroxycarbamide is given to lower platelets if >60yrs old or if previous
thrombosis
Myelofibrosis is hyperplasia of megakaryocytes which produce platelet- derived growth factor,

leading to intense marrow fibrosis and myeloid metaplasia (haemopoiesis in the spleen and liver)
leading to massive hepatosplenomegaly
• Presentation: Hypermetabolic symptoms: night sweats, fever, weight loss; abdominal discomfort
due to splenomegaly; or bone marrow failure (low Hb, infections, bleeding)
• Film: Leuko-erythroblastic cells (nucleated red cells); characteristic teardrop RBCS
• Bone marrow trephine for diagnosis
• Treatment: Marrow support - Allogeneic stem cell transplant may be curative in young people
but carries a high risk of mortality
• Prognosis: Median survival 4–5 years.
Hypercoagulable states
Inherited
• Activated protein c (APC) resistance/factor V Leiden: Chief cause of inherited thrombophilia.
o Present in ~5% of the population, although most will not develop thrombosis.
o Usually associated with a single point mutation in factor V (Factor V Leiden), so that
this clotting factor is not broken down by APC
o Risk of DVT or PE is raised 5-fold if heterozygous (50-fold if homozygous)
• Prothrombin gene mutation: Causes high prothrombin levels and thrombosis due to
down-regulation of fibrinolysis, by thrombin-activated fibrinolysis inhibitor.
• Protein C & S deficiency: These vitamin K-dependent factors act together to cleave and
so neutralize factors V & VIII.
o Skin necrosis also occurs (esp. if on warfarin)
o Homozygous deficiency for either protein causes neonatal purpura fulminans —
manifests as blood spots, bruising and discolouration of the skin resulting from
coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation and is
fatal, if untreated.
• Antithrombin deficiency: Antithrombin is a co-factor of heparin, and inhibits thrombin. Less common, a ects 1:500.
o Heterozygotes’ thrombotic risk is greater than protein C or S deficiency by ~4-fold. Homozygosity is incompatible with life.
Acquired Causes:
• 3rd generation progesterones in contraceptive Pills (Desogestrel is an example. Risk of thrombosis is ~doubled with Pills containing this,
vs levonorgestrel. Part of this e ect is due to redcued free protein S found with desogestrel)
• The antiphospholipid syndrome when serum antiphospholipid antibodies are found (lupus anticoagulant ± anticardiolipin antibody),
predisposing to venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss in pregnancy. In most it is a primary
disease, but it is also seen in SLE.
Michael Grant
lOMoARcPSD|4927727

What tests?
• Ask the lab. Do FBC, film, clotting (PT, thrombin time, APTT, fibrinogen) ± APC resistance test, lupus anticoagulant and anticardiolipin
antibodies, and assays for antithrombin and proteins C & S deficiency (± DNA analysis by PCR for the Factor V Leiden mutation if APC
resistance test is +ve, and for prothrombin gene mutation)
Treatment
• Treat acute thrombosis as standard — heparin, then warfarin to target INR of 2–3
• If recurrence occurs with no other risk factors, lifelong warfarin should be considered
o Recurrence whilst on warfarin should be treated by increasing target INR to 3–4
o In antithrombin deficiency, high doses of heparin may be needed so liaise with a haematologist
o In protein C or S deficiency, monitor treatment closely as skin necrosis may occur with warfarin.
Prevention
• Lifelong anticoagulation is not needed if asymptomatic, but advise of risk of VTE with the Pill or HRT, and counsel as regards to the best
form of contraception
• Warn about other risk factors for VTE
• Prophylaxis may be needed in pregnancy, e.g. in antiphospholipid syndrome.
Immunology
Allergic disorders
Antibody deficiency states

Primary antibody deficiencies (PADs) are the most common primary immunodeficiency diseases. They
are a diverse group of disorders which are characterised by various degrees of dysfunctional antibody
production because of disruption of B-cell differentiation.
• Agammaglobulinaemia – The basic defect is the failure of B cell precursors to mature into
antibody-producing cells resulting in severe antibody deficiency. It is of two types:
o X-linked (Bruton's disease, or XLA) - accounts for 85% of cases and results from mutation in the
BTK genes. It only affects boys.
o Autosomal recessive - accounts for the remaining 15% and can result from a number of genetic
mutations.
• Immunodeficiency with low IgG and normal or high IgM (hyper IgM syndromes)
o Patients with hyper IgM syndromes have inability to switch from production of antibodies
of IgM type to antibodies of other types such as IgG, IgA and IgE. Consequently, these
patients have low levels of IgG and IgA but normal or high level of IgM.
• Common variable immunodeficiency (CVID) - This is a relatively frequent form of
immunodeciency (hence the term common), often diagnosed in adults. The degree and type of
deficiency of immunoglobulins and consequently the presentation varies (hence the term variable)
• Selective IgA deficiency - This is relatively common in the Caucasian population and causes no symptoms in many of those affected,
although some may develop significant clinical problems. It is characterised by undetectable levels of IgA in blood and secretions but no
other immunoglobulin deficiencies.
Michael Grant
lOMoARcPSD|4927727

Systemic lupus erythematosus is a multisystemic autoimmune disease in which autoantibodies are
made against a variety of autoantigens (eg ANA)
• Immunopathology results in polyclonal B-cell secretion of pathogenic autoantibodies
causing tissue damage via multiple mechanisms including immune complex formation
and deposition, complement activation and other direct effects
• Prevalence: ~0.2%. F:M ≈9:1, typically women of child-bearing age.
• Commoner in African-Caribbeans, Asians, and if HLA B8, DR2 or DR3 +ve
• ~10% of relatives may be a ected
• It may be ?triggered by EBV
o Remitting and relapsing illness of variable presentation and course
o Typically presenting with non-specific: malaise, fatigue, myalgia and fever
o Other features include: lymphadenopathy, weight loss, alopecia, nail-fold infarcts, non-
infective endocarditis (Libman–Sacks syndrome), Raynaud’s (30%), migraine (40%),
stroke, and retinal exudates
• Immunology:
o >95% are ANA +ve. A high anti-double-stranded DNA (dsDNA) antibody titre is highly
specific, but only +ve in ~60% of cases
o ENA may be +ve in 20–30% (anti-Ro, anti-La, anti-Sm, anti-RNP)
o 40% are RhF +ve
o Antiphospholipid antibodies (anticardiolipin or lupus anticoagulant) may also be +ve
o SLE may be associated with other autoimmune conditions: Sjögren’s (15–20%),
autoimmune thyroid disease (5–10%)
• Diagnosis see BOX
• Monitoring activity 3 best tests:
o 1 Anti-dsDNA antibody titres
o 2 Complement: decreased C3, C4 (denotes consumption of complement, hence C3d
and C4d, their degradation products, are up)
o 3 ESR. Also: BP, urine for casts or protein (lupus nephritis, below), FBC, U&E, LFTs, CRP
(usually normal)
o Skin or renal biopsies may be diagnostic
o Drug-induced lupus Causes (>50 drugs) include isoniazid, hydralazine (if >50mg/24h in
slow acetylators), procainamide, quinidine, chlorpromazine, minocycline, phenytoin. It
is associated with antihistone antibodies in ~100%
§ Skin and lung signs prevail (renal and CNS are rarely affected)
§ The disease remits if the drug is stopped.
o Sulfonamides or the oral contraceptive pill may worsen idiopathic SLE.
• Management should be through specialist SLE and lupus nephritis clinics
o Severe flares: Acute SLE (eg haemolytic anaemia, nephritis, severe pericarditis or CNS
disease) requires urgent IV cyclophosph amide + high-dose prednisolone
o Cutaneous symptoms: treat rashes with topical steroids. Prevent rashes with high-
factor sunblock creams
§ Sun exposure may also trigger acute systemic flares
o Maintenance: use NSAIDS and hydroxychloroquine for joint and skin symptoms
o Low-dose steroids may be of value in chronic disease
§ Azathioprine, methotrexate and mycophenolate are used as steroid-sparing agents
o Lupus nephritis: May require more intensive immunosuppression with steroids and
cyclophosphamide or mycophenolate.
o BP control is vital: ACE-i, alpha-blockers (eg doxazosin) or Ca2+-channel blockers (eg
nifedipine).
o Renal replacement therapy (p298) may be needed if disease progresses; nephritis recurs in
~50% post-transplant, but is a rare cause of graft failure
• Prognosis is ~80% survival at 15 years. There is an increased long-term risk of cardiovascular
disease and osteoporosis
• Antiphospholipid syndrome can be associated with SLE (20–30%)
o More often it occurs as a primary disease
o Antiphospholipid antibodies (anticardiolipin & lupus anticoagulant) cause CLOTS:
§ Coagulation defect
§ Livedo reticularis (mottled reticulated
vascular pattern that appears as a lace-like
purplish discoloration of the skin due to
backlog of venules from clots)
§ Obstetric (recurrent miscarriage)
§ Thrombocytopenia (consumptive) – There is
a thrombotic tendency, affecting the
cerebral, renal and other vessels
• Rx: Low-dose aspirin, or warfarin if
recurrent thromboses (aim INR of 2–3)
Michael Grant
lOMoARcPSD|4927727

Sjőgren’s disease is a chronic inflammatory autoimmune disorder, which may be primary (F:M ≈9
:1, onset 4th–5th decade) or secondary, associated with connective tissue disease (eg RA, SLE,
systemic sclerosis)
o There is lymphocytic infiltration and fibrosis of exocrine glands, especially lacrimal and
salivary glands
o Features: reduced tear production (dry eyes, keratoconjunctivitis sicca), salivation
(xerostomia—dry mouth, caries), parotid swelling.
o Other glands are affected causing vaginal dryness, dyspareunia, dry cough and
dysphagia
o Systemic signs include polyarthritis/arthralgia, Raynaud’s, lymphadenopathy,
vasculitis, lung, liver and kidney involvement, peripheral neuropathy, myositis and
fatigue
o It is associated with other autoimmune diseases (eg thyroid disease, autoimmune hepatitis,
PBC) and an risk of non- Hodgkin’s B-cell lymphoma
o Tests:
o Schirmer’s test measures conjunctival dryness (<5mm in 5min is +ve)
o Rose Bengal staining may show keratitis (use a slit-lamp)
o Anti-Ro (SSA; in 40%) & anti-La (SSB; in 26%) antibodies may be present (in pregnancy,
these cross the placenta and cause fetal congenital heart block in 5%)
o ANA is usually +ve (74%); rheumatoid factor is +ve in 38%
o There may be hypergammaglobulinaemia
o Rx: Treat sicca symptoms: eg hypromellose (artificial tears), frequent drinks, sugar-free
pastilles/gum.
o NSAIDS and hydroxychloroquine are used for arthralgia
o Immunosuppressants may be indicated in severe systemic disease
Polymyositis & dermatomyositis are rare conditions are characterized by insidious onset of
progressive symmetrical proximal muscle weakness and autoimmune-mediated striated
muscle inflammation (myositis), associated with myalgia ± arthralgia
o Muscle weakness may also cause dysphagia, dysphonia (i.e. poor phonation, not
dysphasia), or respiratory weakness.
o The myositis (esp. in dermatomyositis) may be a paraneoplastic phenomenon, commonly
from lung, pancreatic, ovarian or bowel malignancy
o Dermatomyositis features myositis plus skin signs:
§ Macular rash (shawl sign is +ve if over back & shoulders)
§ Lilac-purple (heliotrope) rash on eyelids often with oedema
§ Nail fold erythema (dilated capillary loops)
§ Gottron’s papules: Roughened red papules over the knuckles, also seen on
elbows and knees (pathognomonic if CK raised + muscle weakness)
§ Subcutaneous calcifications
o Extra-muscular signs in both conditions include fever, arthralgia, Raynaud’s, interstitial
lung fibrosis and myocardial involvement (myocarditis, arrhythmias)
o Tests:
o Muscle enzymes (ALT, AST, LDH, CK & aldolase) raised in plasma
o Electromyography (EMG) shows characteristic fibrillation potentials
o Muscle biopsy confirms the diagnosis (and excludes mimicking conditions)
o MRI shows muscle oedema in acute myositis.
o Autoantibody associations: anti-Mi2, anti-Jo1 — associated with a syndrome of acute onset
and interstitial lung fibrosis that should be treated aggressively
o Differential diagnoses: Carcinomatous myopathy, inclusion-body myositis, muscular
dystrophy, PMR, endocrine/metabolic myopathy (e.g. steroids), rhabdomyolysis,
infection (eg HIV), drugs (penicillamine, colchicine, statins or chloroquine)
o Management Screen systematically for malignancy
o Start prednisolone (eg 1mg/ kg/d PO)
o Immunosuppressives and cytotoxics are used early in resistant cases, eg
azathioprine, methotrexate, cyclophosphamide or ciclosporin
o Hydroxychloroquine or topical tacrolimus may help with skin disease.
Systemic vasculitis
Vasculitis is defined as an inflammatory disorder of blood vessel walls, causing destruction
(aneurysm/rupture) or stenosis. It can affect the vessels of any organ, and presentation
depends on which organs are involved. It may be a primary condition or secondary to
other diseases, eg SLE, RA, hepatitis B & C, HIV. It is categorized according to the main size
of blood vessel affected:
• Large: Giant cell arteritis, Takayasu’s arteritis
• Medium: Polyarteritis nodosa, Kawasaki disease
• Small:
Michael Grant
lOMoARcPSD|4927727

o ANCA +ve vasculitis has a predilection for respiratory tract
and kidneys. It includes p-ANCA associated microscopic
polyangiitis, glomerulonephritis and Churg- Strauss
syndrome, and c-ANCA associated Wegener’s
granulomatosis
o ANCA –ve vasculitis includes Henoch-Schönlein purpura,
Goodpasture’s syndrome and cryoglobulinaemia
• Symptoms:
o Presentation may often be of only overwhelming fatigue
with ฀ESR/CRP
• Tests:
o ESR/CRP
o ANCA may be +ve
o Creatinine if renal failure
o Urine: proteinuria, haematuria, casts on microscopy
o Angiography ± biopsy may be diagnostic
• Management:
o Large-vessel vasculitis: steroids in most cases
o Medium/small: standard therapy is steroids and IV cyclophosphamide
§ Azathioprine may be useful as steroid-sparing maintenance treatment
• Giant cell arteritis (GCA) = cranial or temporal arteritis
o It is common in the elderly—consider Takayasu’s if under 55yrs
o It is associated with Polymyalgia rheumatic in 50%
o Symptoms: Headache, temporal artery and scalp tenderness (eg when combing
hair), jaw claudication, amaurosis fugax
§ Extracranial symptoms may include dyspnoea, morning stifness, and
unequal or weak pulses
§ If you suspect GCA, do ESR and start prednisolone 60mg/d PO
immediately
§ The risk is irreversible bilateral visual loss, which can occur suddenly if not treated
o Get a temporal artery biopsy within 7 days of starting steroids
§ Skip lesions occur, so don’t be put off by a negative biopsy (up to 10%)
o Prognosis: Typically a 2-year course, then complete remission. Reduce prednisolone once symptoms have resolved
o Give gastric and bone protection (PPI & bisphosphonate)
o Associated with polymyalgia rheumatic (neck, shoulder and hip stiffness [esp. in morning] seen in the eldery with reasied ESR and
CRP – Rx: low dose steroids)
• Polyarteritis nodosa (PAN) is a necrotizing vasculitis that causes aneurysms and thrombosis in medium-sized arteries, leading to
infarction in affected organs, with severe systemic symptoms
o It may be associated with hepatitis B, and is rare in the UK
o Symptoms: Typically systemic features, plus predominantly
skin (rash and ‘punched out’ ulcers), renal (main cause of
death, though glomerulonephritis is not seen), cardiac, GI and
GU involvement.
§ Coronary aneurysms occur in Kawasaki disease
(childhood PAN variant)
o Tests: Often WCC, mild eosinophilia (in 30%), anaemia, ESR,
CRP, ANCA –ve.
o Renal or mesenteric angiography, or renal biopsy can be
diagnostic.
o Treatment: Control BP meticulously. Refer to experts.
§ Most respond to corticosteroids and cyclophosphamide
§ Hepatitis B should be treated with an antiviral after initial
treatment with steroids
• Microscopic polyangiitis is a necrotizing vasculitis affecting
small- and medium-sized vessels
o Symptoms: Rapidly progressive glomerulonephritis usually
features; pulmonary haemorrhage occurs in up to 30%; other
features are rare.
o Tests: pANCA (MPO) +ve
o Treatment: As for PAN.
Acquired immune deficiency syndrome

Human immunodeficiency virus (HIV)
• HIV1, a retrovirus, is responsible for most HIV infections
o Virology RNA retrovirus; HIV1 has 9 subtypes or ‘clades’
• HIV2 causes a similar illness (?longer latent period)
Michael Grant
lOMoARcPSD|4927727

• Immunology HIV binds, via its gp120 envelope glycoprotein, to CD4 receptors on helper T
lymphocytes, monocytes, macrophages, and neural cells
o CD4 +ve cells migrate to the lymphoid tissue where the virus replicates, producing billions of new
virions. These are released, and in turn infect new CD4 +ve cells. As infection progresses depletion or
impaired function of CD4 +ve cells reduce immune function
o After cell entry, viral reverse transcriptase enzyme makes a DNA copy of the RNA genome. The
viral integrase enzyme then integrates this into host DNA.
o The core viral proteins are initially synthesized as big polypeptides that are cleaved by viral
protease enzymes into the enzymes and building blocks of the virus.
o The completed virions are then released by budding. The number of circulating viruses (viral load)
predicts progression to AIDS
• Stages
o Seroconversion (primary infection) may be accompanied by a transient illness 2–6wks after
exposure: fever, malaise, myalgia, pharyngitis, maculopapular rash or meningoencephalitis (rare)
o A period of asymptomatic infection follows but 30% have persistent generalized
lymphadenopathy (PGL), defined as nodes >1cm diameter at ≥2 extra-inguinal sites, persisting for
3 months or longer
o Later, constitutional symptoms develop: T°, night sweats, diarrhoea, weight loss, ± minor
opportunistic infections, eg oral candida, oral hairy leucoplakia, herpes zoster, recurrent herpes
simplex, seborrhoeic dermatitis, tinea.
§ This collection of symptoms and signs is referred to as the AIDS-related complex (ARC) and is
regarded as a prodrome to AIDS.
§ AIDS: HIV + an indicator disease (see complications below)
o Time-scales: HIV to AIDS ≈ 8yrs; ARC to AIDS ≈ 2yrs; AIDS to death ≈ 2yrs (without HARRT)
• Diagnosis:
o Serum (or salivary) HIV-Ab by ELISA, eg confirmed by Western blot.
o In recent infection, HIV-Ab might be –ve (window period ~1–3wks after exposure); here, checking
HIV RNA (PCR) or core p24 antigen in plasma, or repeating ELISA at 6wks and 3 months confirms
diagnosis.
• Prevention:
o Blood screening; disposable equipment; antenatal antiretrovirals if HIV+ve ± Caesarean birth ±
bottle-feeding
• Complications: For TB; HHV-8/Kaposi’s sarcoma; for Leishmaniasis.
o Pulmonary
§ The lung is the most vulnerable organ; in developed countries bacterial pneumonia (esp.
pneumococcal) is commonest; elsewhere it is TB and Pneumocystis jiroveci pneumonia the
chief life-threatening fungal opportunistic infection (others: aspergillus, cryptococcus,
histoplasma)
§ Suspect it in anyone with cough/breathlessness or pneumothorax. CXR may be normal; CT:
diffuse ground-glass opacity, consolidation, nodules, cysts.:
§ Treatment: high-dose co-trimoxazole; special monitoring must be available; precede each dose by
prednisolone 50mg
§ Other pathogens: M. avium intracellulare (MAI); CMV
§ Also: HHV-8 (Kaposi’s sarcoma, lymphoma) and lymphoid interstitial pneumonitis.
o Gut
§ Oral pain may be caused by candidiasis, HSV or aphthous ulcers, or tumours.
§ HSV and CMV also cause oesophageal ulcers (similar to Candida).
§ Anorexia/weight loss is common and hepatomegaly from viral hepatitis, sclerosing cholangitis, drugs or MAI.
§ MAI causes fever, night sweats, malaise, anorexia, weight loss,
abdominal pain, diarrhoea, hepatomegaly, and anaemia.
• Treatment: ethambutol + clarithromycin + rifabutin
§ Perianal disease may be from recurrent HSV ulceration, perianal warts,
squamous cell cancer (rare).
§ Kaposi’s sarcoma and lymphomas can also affect the gut.
o Eye
§ CMV retinitis (acuity loss ± blindness) may affect 45% of those with AIDS
• Fundoscopy: characteristic ‘mozzarella pizza’ signs,
• Treatment: Ganciclovir-containing intra-ocular implants (NB: risk of
post-op retinal detachment, one implant does not prevent disease
in the other eye.)
o CNS
§ Acute HIV is associated with transient meningoencephalitis,
myelopathy, and neuropathy
§ Chronic HIV-associated neurocognitive disorder (HAND) comprises
dementia and various encephalopathies (PML)
§ Toxoplasma gondii is the main CNS pathogen in AIDS, presenting with focal signs
• CT/MRI shows ring-shaped contrast enhancing lesions. Treat with pyrimethamine (+folinic acid) + sulfadiazine or
clindamycin for 6 months.
Michael Grant
lOMoARcPSD|4927727

§ Cryptococcus neoformans causes a chronic meningitis, eg with no neck sti ness.
§ Tumours affecting the CNS include primary cerebral lymphoma, B-cell lymphoma; CSF JC virus PCR is useful in distinguishing
PML from lymphoma.
o Psychological complications HIV is the paradigm of a biopsychosocial illness. HIV is 100% preventable, yet very prevalent.
o Farrant’s injunction to HIV doctors: Extension of life without efforts to address patients’ quality of life is not ethical.2
• Pre- & post-exposure prophylaxis (PReP/PEP)
o Seroconversion post-needle-stick: ~0.4% (HIV); 30% for hep B if HBeAg +ve.
§ Wash well. If needle-stick, encourage bleeding; do not suck or immerse in bleach. Report incident to occupational health and fill
in an accident form. Counsel and test recipient at 3 and 6 months.
§ PEP is not indicated after low risk exposures (eg urine, vomit, saliva,
faeces, unless they are visibly bloodstained)
§ Start PEP as soon as possible (certainly within 48–72h), and continue for
≥28d. PEP is not needed if exposure >72h ago. Do follow-up testing at
12 and 24wks post- (or 24wks after cessation of PEP) and continue for at
>12wks after the HIV exposure event (or for at least 12wks from when
PEP was stopped)
§ Starter regimen: One Truvada® tab (245mg tenofovir and 200mg
emtricitabine) once a day plus two Kaletra® film-coated tabs (200mg
lopinavir and 50mg ritonavir) twice a day. Truvada® + Kaletra® is the
preferred regimen, but Combivir® + Kaletra® may be considered as
an option if there are di culties sourcing starter packs containing
Truvada®. 247 
o Acute seroconversion Early identification matters! Signs are like
infectious mononucleosis (eg lymphadenopathy, myalgia, rash,
headache; rarely meningitis); do tests if there are unusual signs, eg oral
candidiasis, recurrent shingles, leucopenia, or CNS signs
o Other direct effects of HIV Osteoporosis; dementia (the brain is a
sanctuary for HIV—and HAART may not prevent dementia from
developing)
MSK/Rheumatology (the bare bones)

Inflammatory arthritis
Acute inflammatory arthritis:

• Usually a monoarthritis
• Typical causes:
o Septic arthritis can destroy the joint within 24hrs
§ Risks: pre-existing joint disease (esp. rheumatoid), DM,
immunocompromised, artificial joint, IVDU, injury
§ Investigations: Joint aspiration + MC&S, x-rays (2 planes)
§ Treatment: If in doubt start empirical IV antibiotics (after aspiration)
until sensitivities are known. Common causative organisms are
Staph. aureus, streptococci, Neisseria gonococcus and Gram –ve
bacilli. Follow local guidelines for antibiotic choice:
• Consider flucloxacillin 1g/6h IV (clindamycin if penicillin
allergic); vancomycin 1g/12h IV if MRSA (or history of MRSA)
• Ask for orthopaedic advice for consideration of arthrocentesis,
lavage and debridement, esp. if there is a prosthetic joint
o Crystal:
§ Gout (NSAIDs, Colchicine followed by allopurinol 1/12 after acute)
§ Pseudogout
o Blood (haemarthrosis – haemophilia, warfarin)
o Rarer: reactive arthritis, psoriatic, sarcoidosis
Chronic inflammatory arthritis:

• Establish if inflammatory or degenerative:
o Inflammatory:
§ Early morning stiffness (>30 minutes)
§ Worse on rest
§ Soft tissue thickening
o Degenerative:
§ Night pain
§ Worse on use
§ Crepitus
§ Bony thickening
Michael Grant
lOMoARcPSD|4927727

Rheumatoid Arthritis is a chronic systemic inflammatory disease, characterized by a
symmetrical, deforming, peripheral polyarthritis.
• HLA DR4/DR1 linked (associated with increased severity).
• Presentation:
o Typically: symmetrical swollen, painful, and stiff small joints of hands and feet, worse
in the morning
o Less common presentations:
§ Sudden onset, widespread arthritis
§ Recurring mono/polyarthritis of various joints (palindromic RA);
§ Persistent monoarthritis (often knee, shoulder or hip)
§ Systemic illness with extraarticular symptoms, eg fatigue, fever, weight loss,
pericarditis and pleurisy
§ Polymyalgic onset — vague limb girdle aches
§ Recurrent soft tissue problems (eg frozen shoulder, carpal tunnel syndrome,
deQuervain’s tenosynovitis).
• DeQuervain’s tenosynovitis (a.k.a. Gamer’s thumb) – is a tenosynovitis of
the sheath that extend plicis - Finkelstein's test (ulnar movement of closed
fist)
• Signs:
o Early (inflammation, no joint damage): swollen MCP, PIP, wrist, or MTP joints
(often symmetrical)
§ Look for tenosynovitis or bursitis
o Later (joint damage, deformity): ulnar deviation of the fingers and dorsal wrist
subluxation
§ Boutonnière and swan-neck deformities of fingers or Z-deformity of thumb)
extensor tendons may rupture. Foot changes are similar. Larger joints can be involved
§ Atlanto-axial joint subluxation may threaten the spinal cord (rare) and poses difficult airway – can trigger massive vagal outflow
that causes asystole
o Extra-articular:
§ Nodules esp. elbows & lungs (collagenous granulomas)
§ Vasculitis + accelerated atherosclerosis (manage risk
factors)
§ Fibrosing alveolitis (lower lobe) +/- pleural & pericardial
effusion;
§ Raynaud’s;
§ Carpal tunnel syndrome
§ Splenomegaly (Felty’s syndrome: RA + splenomegaly +
neutropenia,)
§ Episcleritis, scleritis, scleromalacia, keratoconjunctivitis
sicca (dry eyes) – secondary Sjogren’s
§ Osteoporosis
§ Amyloidosis (secondary)
§ Anaemia of chronic disease (micro/normocytic, reduced TIBC)
• Investigations:
o Rheumatoid factor (RhF) is positive in ~70%; A high titre is associated with severe
disease, erosions and extra-articular disease
o Anticyclic citrullinated peptide antibodies (anti-CCP) are highly specific (~98%) for
RA.
o Rasied ESR and CRP
o X-rays show soft tissue swelling, juxta-articular osteopenia and joint space loss;
Later there may be bony erosions, subluxation or complete carpal destruction
§ Presents of pannus (a layer of vascular fibrous tissue extends over the joint
surface)
o Ultrasound and MRI can identify synovitis more accurately, and have greater
sensitivity in detecting bone erosions
• Management:
o Disease activity is measured using the DAS28 - Aim to reduce score to <3
o Early use of DMARDS and biological agents improves long-term outcomes
o Steroids rapidly reduce symptoms and inflammation - are useful for treating acute
exacerbations (‘flares’), eg IM depot methylprednisolone 80–120mg. Intra-articular
steroids have a rapid but short-term effect
o First line: NSAIDs
§ Treats symptoms but doesn’t deal with disease progression
§ Co-prescribe PPI or consider COX-2 (celecoxib)
o Second line: DMARDs
§ Methotrexate
§ Leflunomide (inhibits dihydroorotate dehydrogenase needed for DNA)
§ Sulfasalazine (5-ASA; also used in IBD, reasons why effective in various forms of
arthritis is not clearly understood - thought to work by inhibiting NF-κB)
§ Older drugs: Gold (S/E: Blue skin discolouration), Penicillamine,
o Third line: Biologics (esp. if DAS28 of >5.1 – but note S/E)
Michael Grant
lOMoARcPSD|4927727

§ Anti-TNF – e.g. infliximah (IV) or humera (SC)
§ Anti-IL-1 – e.g. anakinra
§ T-B/APC co-stimulation inhibitor – Abatacept
Osteoarthritis is the commonest joint condition caused by wear

and failure of hyaline cartilage that leads to a painful loss of
function
• Usually primary
o Generalized – genetic component through enes that
encode hyaline GAGs (seen as increased water content – 90% rather
than 65%) and greater activity of metalloproteinases
• May be secondary to joint disease (trauma, RA) or other conditions (eg
haemochromatosis, obesity, collagen defect)
• Signs and symptoms:
o Localized disease (usually knee or hip): pain on movement and
crepitus, worse at end of day; background pain at rest; joint gelling—
stiffness after rest up to ~30min; joint instability
o Generalized disease (primary OA): with Heberden’s nodes (‘nodal
OA’, usually post-menopausal ), DIP joints, thumb carpo-metacarpal
joints and the knees.
§ Joint tenderness, derangement and bony swelling (Heberden’s
nodes at DIP, Bouchard’s nodes at PIP), reduced range of movement and mild
synovitis
• Tests: Plain radiographs show: Loss of joint space, Osteophytes, Subarticular sclerosis and
Subchondral cysts; CRP may be slightly elevated in mild synovitis
• Management:
o Core treatments: Exercise to improve local muscle strength and general aerobic fitness
§ Weight loss if overweight
o Analgesia: Regular paracetamol ± topical NSAIDS; add codeine or short-term oral
NSAID (+PPI) if resistant
§ Intra-articular steroid injections temporarily relieve pain in severe symptoms
§ Intra-articular hyaluronic acid injections (very expensive)
o Surgery: Joint replacement (hips, or knees) is the best way to deal with severe OA
Spondyloarthritides:
• Usually affect the large joints of the lower limb
• Often with sacrolitis and enthesitis
• May have Hx of psoriasis & IBD
• All linked to the MHC gene HLA-B27
• Extra-articular features:
o Eyes:
§ Iritis (ant. uveitis – may lead to synechia; an eye
condition where the iris adheres to either cornea
or lens)
§ Conjunctivitis
o Skin:
§ Psoriasis
§ Keratoderma blenorrhagicum (scaly lesions occur
on the palms/soles, very similar to pustular psoriasis);
seen also in reactive arthritis)
§ Geographic tongue
§ Circinate balanitis (dermatitis of the glans penis)
o Pulmonary fibrosis (upper lobe) +/- effusion
o Aortic incompetence
• Ankylosing spondylitis
o The typical patient is a man <30yrs old with gradual onset of low back pain,
worse at night, with spinal morning stiffness relieved by exercise
o Pain radiates from sacroiliac joints to hips/buttocks, and usually improves
towards the end of the day
o There is progressive loss of spinal movement (all directions)—hence
reduced thoracic expansion.
o Tests:
§ Examination:
• Reduced flexion
• Reduced lordosis (+ve Thomas test)
• Flexed neck
• Aortic incompetence (collapsing pulse)
§ Imaging:
• Sacroiliac changes
Michael Grant
lOMoARcPSD|4927727

• Syndesmophytes between vertebrae (bamboo spine)
• Romanus lesion (shiny corner on MRI due to cell turnover)
o Management:
§ Exercise, not rest, for backache, including intense exercise regimens to maintain
posture and mobility—ideally with a physiotherapist specializing in AS.
§ NSAIDS (eg ibuprofen or naproxen, if no CI) usually relieve symptoms within 48h,
and may slow radiographic progression
§ TNF blockers etanercept, adalimumab and golimumab are indicated in severe
active AS if NSAIDS fail
Crystal arthopathies:
• Gout is caused by the precipitation of monosodium urate crystal, which attacks occurs in
phases: asymptomatic hyperuricaemia > acute attacks > polyarticular >chronic tophaceous
o Typically presents with an acute monoarthropathy with severe joint inflammation
o >50% occur at the metatarsophalangeal joint of the big toe (podagra)
o Hyperuricaemia can be caused by:
§ Reduced excretion – alcohol, diuretics (thiazide), CKD
§ Increased production – leukaemia, obesity, psoriasis
§ Increased purine intake – liver, oily fish, asparagus
o Triggers can include: trauma, drugs, stress, dehydration
o Investigations
§ Aspiration with Polarized light microscopy of synovial fluid shows negatively
birefringent urate crystals
§ Serum urate is usually raised but may be normal
§ Radiographs show only soft-tissue swelling in the early stages. Later, well-defined
‘punched out’ erosions are seen in juxta-articular bone
o Treatment of acute gout Use high-dose NSAID or coxib; Symptoms should subside
in 3–5d
§ If CI (eg peptic ulcer; heart failure; anticoagulation), colchicine (0.5mg/6–12h PO)
is e ective but slower to work
§ If getting more than 1 attack a year, consider prevetion with allopurinol
• Calcium pyrophosphate disease involves the intra- and extra-articular deposition of CPPD
crystals and is seen as any of:
o Acute CPP crystal arthritis (previously pseudogout)
can be provoked by illness, surgery or trauma and
typically affects larger joint on presentation than true
gout
o Chronic CPPD inflammatory RA-like (symmetrical)
polyarthritis
o Osteoarthritis with CPPD superimposed
o Risk factors: Old age, hyperparathyroidism,
haemochromatosis hypophosphataemia (relatively
high free Ca).
o Tests
§ Aspiration with polarized light microscopy of
synovial fluid shows weakly positively birefringent
crystals in pseudogout
§ Soft tissue calcium deposition – chondrocalcinosis – on x-ray
o Management
§ Acute attacks: cool packs, rest, aspiration and intra-articular steroids
§ NSAIDS (+PPI) ± colchicine 0.5–1.0mg/24h (used with caution) may prevent acute attacks
• Methotrexate and hydroxychloroquine have a role in chronic CPPD
Foot pathologies:
• Normal Gait take the form for 3 rockers:
o Heel rocker: the heel is the fulcrum as the foot rolls into plantar flexion.
The pretibial muscles eccentrically contract to decelerate the foot drop
and pull the tibia forward
o Ankle rocker: the ankle is the fulcrum and the tibia rolls forward due to
forward momentum. The soleus eccentrically contracts to decelerate the
forward progression of the tibia over the talus. Ankle and forefoot rocker
can be compromised by imbalances in strength and length of the
gastroc/soleus group and anterior compartment muscles.
o Forefoot rocker: tibial progression continues and the gastroc/soleus
groups contract to decelerate the rate of forward limb movement. This,
along with forward momentum, passive tension in the posterior
compartment muscles, active contraction of the posterior compartment
and windlass effect of the plantar fascia results in heel lift.
• Shape pathology
o Pes planus is a flat foot (mild valgus) and is either fixed or flexible
Michael Grant
lOMoARcPSD|4927727

§ To test, ask patient to stand on tip toes and if valgus corrects
then it is flexible
o Pes cavus is a high arched foot with mild vargus
§ Coleman’s block test: edge of foot on block and if varus correct,
then it is a mobile joint
o Skewfoot is a hindfoot valgus deformity with forefoot adduction
o Metatarsus adductus is a normal hindfoot with a forefoot adduction
o Toes:
Bone tumours can be either:

• Primary
o Typically present with pain and swelling
o Usually form in areas of bone growth
o Rare and usually in younger patient from genetic cause
o Benign:
§ Osteoid osteomas are small lesions of long bones that possess no
malignant risk and cause night pain
§ Osteochondromas are cartilage-capped exostosis (benign bone growth of
the surface of another bone)
§ Enchondroma are cartilaginous lesions within the medulla (also seen on
hands)
§ Giant cell tumours are benign but can cause serious damage:
• Located in the epiphysis, thus complete excision is impossible
• On histology they are seen with multi-nucliated giant cells that can
produce osteoid
• Many mitotic figure but not truly malignant
o Malignant:
§ Osteosarcoma is the most common primary malignant
• Any malignant tumour that produces osteoid
• Usually intra-medullary
• High grade
§ Ewing’s Sarcoma is a high grade tumour derived from primitive
neuroectoderm
• Made up of small, round, blue cells (same origin as SCLC)
• Affects the diphysis of long bones
• On xray there is periosteal reaction and soft tissue mass
§ Chondrosarcoma
• Difficult to differentiate from benign enchrondroma
• Unlike other types of malignant bone cancer, it does not respond well to chemo- radio-therapies
• Only treatment is surgery; which can be difficult to achieve good margins in certain locations, so there is a risk of local
recurrence – not to mention deformity
• Secondary
o Present with pain and pathological #
o Account for the vast majority (almost exclusively in the >30yo) and are usually mets from breast, lung, kidney, prostate, thyroid or
myeloma
§ Batson venous plexus (Batson veins) is a network of valveless veins in the
human body that connect the deep pelvic veins and thoracic veins (draining
the inferior end of the urinary bladder, breast and prostate) to the internal
vertebral venous plexuses providing route for the spread of cancer metastases
Systemic sclerosis is a connective tissue disase that cuases small vessel damage (endothelial
damage>myointimal proliferation>decreased lumen) and fibrosis (via increase fibroblast
activity). It has the features of scleroderma (skin fibrosis) and vascular disease:
• Limited cutaneous systemic sclerosis: (formerly CREST syndrome) Calcinosis
(subcutaneous tissues), Raynaud’s, oesophageal and gut dysmotility, Sclerodactyly
(swollen tight digits), and Telangiectasia.
o Skin involvement is ‘limited’ to the face, hands and feet
§ Face: macrosomia (3 finger test), beaked nose
o It is associated with anticentromere antibodies in 70–80% (Crest – centromere)
Michael Grant
lOMoARcPSD|4927727

o Pulmonary hypertension is often present subclinically, and can
become rapidly life- threatening, so should be looked for
§ Rx: Sildenafil (potent and selective inhibitor of cGMP-specific
phosphodiesterase type 5 (PDE5), which is responsible for
degradation of cGMP; which causes prolonged smooth muscle
dilation), bosentan (competitive antagonist of endothelin-1 at the
endothelin-A (ET-A) and endothelin-B (ET-B) receptors that are
normally responsible for vasocontriction)
• Diffuse cutaneous systemic sclerosis:
o ‘Diffuse’ skin involvement (whole body in severe cases) and early organ
fibrosis:
§ Lung – fibrosis leads to pulmonary hypertension
§ Cardiac – pericarditis, cardiomyopathy
§ GI – dysphagia, malabsorption
§ Renal - Renal crisis’ presents with AKI + accelerated hypertension
• Rx: ACE-i if raised BP or in renal crisis; dialysis or transplant
may be required
o Antitopoisomerase-1 [Anti-Scl70] antibodies in 40% and anti-RNA polymerase in 20%
o Other investigations:
§ Nail bed ophthalmoscopy for telangiectasia
o Prognosis is often poor
o Control BP meticulously.
o Management: Currently no cure
§ Immunosuppressive regimens, including IV cyclophosphamide, are used for organ involvement or progressive skin disease.
§ Regular ACE-i or ARBS to reduce risk of renal crisis
§ Raynaud’s phenomenon: ?IV prostacyclin
§ Mixed connective tissue disease combines features of systemic sclerosis, SLE and polymyositis. Debate continues as to
whether this is a distinct disease.
Dermatology
Michael Grant
lOMoARcPSD|4927727
Eczema is dermatitis of an intrinsic origin and has varied appearance, but it’s
hallmark is an intense itch. It’s appearance can also be based on its timing:
• Acute eczema is known as wet eczema
o Red, oedematous skin due to erythematous inflammation
o Papules +/- vesicles
• Chronic is known as dry eczema
o Red, thickened skin
o Lichenification (hypertrophied skin with exaggeration of the
normal skin markings; bark-like) +/- fissuring
o Post. Inflammatory pigment changes
• 15-20% of children will have the condition to some degree, but only 3%
of adults
• Pathophysiology of the condition involves a primary defect in the
barrier function of the skin, leading to:
o Increased water loss
o Increased sensitivity to infection, sweating/heat, allergens, irritants
o Scratch-itch cycle leads to more inflammation, excoriation and
lichenification
• Clinical subtypes:
o Intrinsic:
§ Atopic
§ Seborrhoeic
§ Discoid
§ Pompholyx (intensely itchy watery blisters, restricted to the
hands and feet)
§ Varicose eczema (seen with PVD)
o Extrinsic:
§ Contact irritant dermatitis
§ Contact allergic dermatitis
• Atopic eczema tends to be associated with hayfever and asthma (the
atopic march) and is the most common cause of eczema
o Typically seen on the flexural surfaces with some variations with
age; children tend to have on face whereas adults hands/feet
o Triggers:
§ Stress/heat/sweat
§ Stratching
§ Infection:
• Staphlycoccal – Impetigo (Rx: topical fusidic acid, ?Flucloxacillin/erythromycin if extensive)
o Seen with golden crust – remember to take swab
• Herpes – eczema herpeticum (Rx: acyclovir)
o Pain rather than usual itch can be clue
o Admit anyone with suspected infection with herpes simplex virus (eczema herpeticum) esp.
with eye involvement as is can spread to conjunctiva and cause scarring
• Molluscum contagiosum (self-limiting viral infection)
o Dome-shaped papules on flexural surfaces
• HPV – warts
§ Irritants (soap, wool, face cream, pet dander)
o DDx: scabies, contact dermatitis, psoriasis, seborrheic
eczema, drug s/e, mycosis fungoides [cutaneous T-cell
lymphoma])
o Rx:
§ Maintenance: Emollients and soap substitutes
§ Breakthrough:
• Topical steroids in a “ladder fashion” – risk of skin
thinning, bruising, stretch marks, folliculitis and
pimples, loss of skin pigment, and hair growth;
esp. face (risk of rosacea too), neck, genitals,
axillae
o Rarely can cause Cushing’s
o Finger Tip Unit (about 500mg) is the amount
of medication needed to squeeze a line from
the tip of an adult finger to the first crease of
the finger. It should be enough to treat an
area of skin double the size of the flat of your
hand with your fingers together
Michael Grant
lOMoARcPSD|4927727

o Different strengths: mild (dioderm), moderate (alphaderm), potent (dermovate)
• Topical calcineurin inhibitors (Calcineurin induces different transcription factors (NFATs) that are important in the
transcription of IL-2 genes, which activates T-helper lymphocytes)
o Tacrolimus ointment of different strengths (e.g. Elidel)
§ Adjuvants:
• Antibiotics
• Antihistamines for pruritus
§ Refractory disease:
• Narrow-band UVB phototherapy
• Oral drugs; e.g. steroids, aziothioprine, cyclosporine (calcineurin inhibitors)
§ Non-pharmacological therapies:
• Dermatology nurse – education and wet wraps (tubifast garments)
• Psychologist – techniques to break scratch-itch cycle
• Support groups
• Seborrhoeic eczema is a common type affect the scalp, t-zone and upper trunk, which
is seen with red/yellow scales that are slightly pruritic (not as much as atopic)
o Associated with yeast overgrowth (Malassezia fungi) thus is seen in
immunosuppressed (e.g. AIDS)
o Rx: Anti-fungals, topical steroids
• Discoid eczema usually affects the limbs with round patches that are intensely itchy
o Rx: Can be difficult to treats so consider potent topical steroids
o DDx: Bowen’s disease, tinea, psoriasis
• Pompholyx aczema is a blistering acute form of that affects the hands and feet – which is linked to hyperhidrosis
• Varicose eczema usually forms in the lower legs of those with venous disease and seen with haemosiderin
deposition
o Can be confused with cellulitis but varicose eczema is almost exclusively bilateral
o The eczema will overlie lipodermatosclerosis
o There is a risk of venous ulceration
o Rx: Emollients and TED stockings (if severe, consider sclerotherapy or venous stripping)
o See surgery notes
• Asteatotic eczema is found in hospitalised elderly patients as areas of very dry
skin (typically on the shins) with crazy paving pattern
o It is not associated with venous insufficiency
o Made worse by soaps and poor nutrition
o Rx: Emollients
• Extrinsic eczema
o Allergic contact dermatitis (a type 4 hypersensitivity i.e. delayed, cell-
mediated [esp. T-Helper] response rather than antibody) is caused by substances that come into contact with
the skin
§ Typical causes are: Nickle, perfume, hair dye
§ Patch testing is performed to identify the exact allergen
§ Avoidance is advised
o Irritant contact dermatitis is typically seen in those that wash their hands very
often or come into contact with chemicals professionally
§ May improve at weekend (i.e. away from occupational exposure)
§ Rx: soap substitutes and emollients
Psoriasis is a common (2%) benign, inflammatory condition that produces plaques with
a range of different clinical patterns
• Triggers:
o Stress
o Alcohol
o Smoking (esp. palmo-plantar)
o Physical trauma (Koebner phenomenon)
o Infection (e.g. Streptococcus > guttate psoriasis)
o Drugs (Lithium, B-blockers, ACE-I, Antimalarials)
o Steroid refound effect
• The pathogenesis is related to a T-cell driven inflammation that leads to a
hyperproliferation of keratinocytes and angiogenesis
• Subtypes:
o Chronic plaque is the classic salmon pink plaques that are seen symmetrically
on extensor surfaces
§ Tends to have some scalp involvement
§ Auspitz sign – removal of a section of plaque will result in pin point
bleeds due to thinning of rete pegs and angiogenesis underneath
§ Rx:
• Topical vitamin D analogues (anti-proliferative, prodifferentiative
and immunomodulatory)
• Tar preparations (SPF afterward due to photosensitivity)
Michael Grant
lOMoARcPSD|4927727

o Except mechanism is unknown but through to inhibit DNA synthesis with
subsequent inhibition of keratinocyte proliferation
• Rarely, topical steroids can be used but only short term due to rebound effects
• UVB photo therapy
• Systemic agents; methotrexate, cyclosporine and biologics
o Methotrexate is given (usually weekly) with folate supplements
§ Good in those also with joint pain
§ Monitor LFTs and look for pulmonary fibrosis
o Ciclosporin is a calcineurin inhibitor
§ Skin only
§ Renal complications can lead to hypertension
o Aceitretin is a vitamin A derivative that binds to nuclear receptors altering
transcription to induce keratinocyte differentiation and reduce epidermal hyperplasia, leading to the slowing of cell
reproduction
§ Used in skin only disease
§ Avoid pregnancy or blood donation for 3 years due to half-life of metabolite
o Biologics
§ Humera/Etanercept/Infliximab (anti-TNFs) are reserved for those with psoriasis with psoriatic arthritics or those
with severe disease
o Erythrodermic psoriasis is a serious condition that affects >90% of a patients with fever and malaise.
§ It is usually seen with:
• Defective thermoregulation
• Fluid/protein loss (may trigger high output cardiac failure)
• Secondary infection
§ DDx:
• Lymphoma, particularly Sézary's syndrome
• Drug eruption - eg, allopurinol, gold, isoniazid, phenytoin, sulfonamides,
sulfonylureas
§ Rx:
• Emollients
• Supportive fluids
• Systemic psoriatic treatments
o Pustular psoriasis is seen as sheets of small pustules that coalesce to give sheets of pus (sterile)
that leave the skin red and sore, along with fever and malaise.
§ The acute, generalised form (Zumbusch) has a mortality of 5-10%
§ Treatment is the small as erythrodermic
o Palmo-plantar psoriasis is seen on the palms and soles with pustules on a background of
erythema resulting in functional impairment from the pain
§ Rx can be difficult::
• Tar
• Potent topical steroids
• Psoralen and ultraviolet A phototherapy (PUVA) or UVB
o Psoralen - given topically – intercalates into DNA and on exposure to ultraviolet
(UVA) radiation can form monoadducts and covalent interstrand cross-links
o Higher risk of skin cancer in the long term
• Systemic treatments
o Guttate psoriasis is a common form seen in teenagers after a streptococcal infection, forming
teardrop plaques
§ It may resolves completely or become chronic psoriasis
§ Rx:
• Vit D + Tar (Dovaobet ointment)
• Tar
• UVB
o Flexural psoriasis affects flexures (not flexural surfaces) such as the axilla, breast and groin.
§ It appears very erythematous with a well-defined edge but does not possess the usual scales
§ Commonly linked to candidiasis
§ Rx: topical steroids + antifungal
• UV Treatments:
o First-line: UVB is given 3 times per week for 6 weeks
§ Limited due to risk of skin aging and cancer
§ Effective in guttate and chronic
o Second-line: Psoralen + UVA (PUVA) is given twice weekly for 6 weeks
§ Effective against all types esp. those with hand and foot involvement
• Complications:
o Arthropathy
§ Enthesitis commonly occurs at the heel of either foot (may be seen as periarticular
erosions and bone resorption giving the appearance of a “pencil in a cup”)
Michael Grant
lOMoARcPSD|4927727

§ Arthritis mutilans a severe form of either PsA or rheumatoid
arthritis caused by marked bony resorption and the co
nsequent collapse of soft tissue; when this affects the hands, it
can cause a phenomenon sometimes referred to as
"telescoping fingers"
§ Dactylitis (Sausage Fingers or Toes)
o Metabolic syndrome
§ Longterm increased CVS risks
§ Improved by methotrexate
o Psychological
§ Depression is common
o Nail dystrophy
§ Oil drop discolouration
§ Pitting
§ Onycholysis (with increased risk of tinea umguium)
o Psoriatic scalp
§ Tar/steroid shampoo
§ Oils can remove scale (esp. coconut)
§ Acitretin useful here
Acne vulgaris is a chronic inflammation of the

pilosebaceous unit (i.e. hair, follicle, erector pilli,
sebaceous gland) that can eventually lead to scarring
• Pathogenesis:
o Increased sebum production
o Hyperkeratosis of the duct
§ Influenced by androgens, those with
acne may be more sensitive to androgens
o Obstruction allows colonisation by
proprionibacterium acnes resulting in
inflammation and formation of pustule
§ Obstructed follicle known as a comedone
which is either:
• Open – known as blackheads
• Closed – known as whiteheads
o Pustules are due to the leak of follicle contents onto the surround skin causing a
superficial inflammation
o Can also form nodules or cysts that cause deep erythema and are very painful
o Scarring: can be hypertrophic (raised red areas) or ice-pick (deeper scars)
• Grading:
o Mild – comedones and small pustules
o Moderate – papulopusular lesions (or mild that hasn’t responded to Rx)
o Severe – nodulocystic lesions (or moderate that hasn’t responded to Rx); tends to
have significant psychological upset
• Treatment:
o Mild:
§ Benzoyl peroxide washes (careful with hair and clothes)
• Azelaic acid is an option if other drugs are poorly tolerated
§ Topical ABx (erythromycin, tetracycline)
§ Topical retinoids (e.g. acitretin)
• May cause photo sensitivity and irritation
o Moderate:
§ Oral ABx for 3 months
• Erythromycin or tetracycline
• Works synergistically with benzoyl peroxide to reduced antibiotic
resistance
§ Oral contraceptive pill
• Specific preparations are good for acne treatment in females, e.g.
Yasmin, Diannette
o Severe:
§ Roaccutane (Isotretinoin) is a vitamin a derivative that reduces the
production of sebum and shrinks the sebaceous glands
• It stabilises keratinization, prevents comedones from forming and
reduces inflammation in moderate/severe acne
• The exact mechanism of action is unknown, however it is known that it alters DNA transcription
§ Taken orally for 4 months
§ S/E: Dry skin/mucosa, hepatitis (no alcohol and monitor LFTs), mood disturbance (?suicide risk)
§ HIGHLY teratogenic; girls must be on OCP and have had recent serum hCG
Michael Grant
lOMoARcPSD|4927727
Acne rosacea is a chronic inflammatory condition seen with crops of papules

and pustules on erythema and telangiectasia
• Usually seen in 30-40yo, females, celtic descent/fair skin
• Pathogenesis is unknown but UV exposure is linked as it can trigger flares
• Can be divided into:
o Pustular Rosacea:
§ Papulopustular lesions with no comedones (thus not acne)
§ Rhinophyma: sebaceous hyperplasia that leads to a large
bulbous nose
§ Occular involvement (50%) can cause blepharitus (eyelid inflam.)
o Erythematous rosacea:
§ Frequent facial flushing leads to persistent flush
§ Triggers include alcohol, spicey food and UV
• Treatment:
o Pustular:
§ Topical metronidazole
§ Oral ABx (Tetra or erythromycin)
§ Plastic surgery for rhinophyma
o Erythematous:
§ UV protection
§ Emollient
§ Avoid triggers – e.g. alcohol
§ Laser therapy for telangiectasia
Skin infections:
Bacterial
• Impetigo is a contagious, crusting infection of the
skin caused by S. Aureus
nd
o Can be 2 ary to ecxema
o Rx: Fusidic acid or flucloxacillin if extensive or
fails to respond
• Cellulitis is an infection of the dermis and sub. cut.
Tissue and is usually caused by S. Aureus or Stept.
Pyogenes.
o Usually unilateral in the lower limbs
o Spreading hot erythema with lymphangitis
o Entry wound may be seen (abrasion, ulcer,
tinea pedis)
o Treat with oral ABx
§ IV if systemic
• Staphylococcal scalded skin syndrome is seen
when a local staph infection release an endotoxin
that causes superficial denudation of the skin at
flexural sites
o Usually seen in children with +ve Nikolski sign
o IV Flucloxacillin
• Folliciulitis/furunculosis are infections of hair follicles that are superficial and deep,
respectively. They produce pustules or abscesses
o Take a swab
o Rx is oral flucloxacillin
o May require prolonged tetracycline if resistant
• Erysipelas is similar to cellulitis but tends to affect the dermis and
superficial sub. cut. Tissues only
o It is seen as a painful erythema that is clearly demarcated
§ Usually caused by strept. Pyogenes
§ High fever and systemic signs, greater than that seen in
cellulits
§ IV Penicillin
• Erythrasma is a form of intertrigo (erythema between 2 opposing areas of skin) caused by
Corynebacterium and it fluoresces under woods light
st nd
o Rx: 1 Fuscidic acid, 2 PO Erythromycin
• Lyme disease is caused by tick bites that allow entry of borrelia burgdorferi (a spirochete), with an infection that occurs
in stages:
o Stage 1: Erythema chronicum migrans (targetoid) at 7 to 10 days
o Stage 2: Lyme disease with headache, malaise and chills
o Stage 3: Chronic arthritis or neurological disease
o Investigate with serum antibody titres to borrelia
o Rx: Oral Tetracycline
Michael Grant
lOMoARcPSD|4927727

• Syphilis is caused by treponema pallidum and is usually
contracted by sexual contact (or congenital)
o Swabs of chancre, serology for antibody and VDRL test
o Rx is penicillin
• Necrotising fasciitis is a soft tissue infection caused by staph, strept

or clostridium, in which bacterial toxin cause thrombosis and necrosis
o Can be precipitated by injury to skin
o Risk from immunosuppreison and nsaids
o Rx: IV ABx and prompt debridement
Fungal infections:
• Candidiasis is caused by candida albicans; a yeast that is found on
the skin
o Infection is usually seen in the immunosuppressed or diabetes
o Types:
§ Mucosal surfaces (esp. tongue, Angular chelitis)
§ Intertrigo/napkin dermatitis
§ Chronic paronychia
o Rx: Topical nystatin (binds to ergosterol) or PO fluconazole
• Pityriasis versicolor is an infection of the torso caused by malassezia furfur – usually triggered by warm, humid
environments
o Causes light brown macules on white skin and vice versa
o Rx: Topical ketoconazole shampoo
• Tinea capitis is a ringworm infection on the scalp caused by the dermatophyte infection that invades the hairshaft
– usually microsporum canis from puppies and kittens
o Rash is similar to that of lyme disease but differs as this is a plaque rather than a patch
o Fluoresces green under woods light
o Kerion is a more advanced form (caused by a more aggressive dermatophyte) that leads to a boggy
mass with hair loss
§ Dx: hair sample with scrapings
§ Rx: Oral Terbinafine (inhibits ergosterol synthesis by inhibiting squalene epoxidase)
• Tinea corporis is a ringworm infection of the body with an itchy rash – as with capitis – which can spread from
tinea ped is or pets
o Dx: Skin scrapings
o Rx: Topical/oral anti-fungals
• Tinea pedis (a.k.a. athlete’s foot) and egins in nail or toes webs then spread to the rest of the foot
o Dx: Skin scrapings
o Rx: Topical anti-fungals
• Tinea unguium is a dermatophyte infection on the nails seen as onychomycosis
o Dx: Nail clipping
o Rx: *Oral* anti-fungals for 3-6 months
Michael Grant
lOMoARcPSD|4927727

Infestations:
• Scabies (Sarcoptes scabei, an arachnid) produces an intensely itchy is spread is commonly in families.
o The patient: Papular rash (on abdomen or medial thigh; itchy at night) + burrows (in digital web
spaces and flexor wrist skin)
§ o Penile lesions produce red nodules
o Incubation: ~6wks (during which time sensitization to the mite’s faeces and/or saliva occurs)
o Dx: Tease a mite out of its burrow with a needle for microscopy (dropping oil and scraping with a
scalpel may provide faeces or eggs)
o Rx: Bedding, clothing, etc. of the patient and close contacts should be decontaminated (eg
washing in hot water and drying in a hot
dryer)
§ Give written advice (OHCS p608)
§ Apply 5% permethrin over whole
body including scalp, face (avoid
eyes), neck and ears (BNF)
• Do not forget the soles
• Wash off after 8–12h; repeat after
7d; use 5% cream on hands if
washed before the 8h elapses
Skin cancer
Benign
• Lentigo is a small pigmented macule/patch due
to hyperplasia of melanocytes typically due to UV exposure, restricted to the epidermis (unlike the “nests” found in
nevi)
o It can rarely turn into lentigo meligna (i.e. melanoma in situ) or even lentigo
maligna melanoma
o Any recent changes should be investigated
• Melanocytic naevi can be either:
o Congenital: since birth and tend to become hairy as a teenager
o Acquired:
§ Junctional are in the epidermis only, thus tend to be brown and flat
§ Compound have both epidermal and dermal parts thus tend to be brown and
raised
§ Dermal have only a dermal component so they will be raised but flesh
coloured
§ Acquired naevi may evolve throughout the lifecycle so monitor and treat with
an ABCDE appraod
• Seborrhoeic keratosis are benign pigmented lesion that tend to have an irregular, stuck-on appearance that usually
occur in groups.
o Often mistaken for melanocytic naevi but tend to occur on non-sun exposed skin (esp. backs)
• Haemangioma are vascular tumours (occasionaly associated enchondromas in Maffucci syndrome) that grow rapidly
after birth but resolve after 12 months, occasionally leaving a scar
o If large or restricting function, treat with propranolol
Premalignant lesions may not always progress to cancer but highlight a high level of UV exposure and should prompt a
full body check.
• Actinic keratosis is an ill-defined keratotic lesion on chronically sun exposed locations
o More common in faired skinned people
o Stress importance of sun protection
o Risk of BCC/SCC
o Rx: Diclofenac gel or cryotherapy
§ Work to increase inflammation to increase detection by bodies own immunesystem
• Bowen’s disease is a squamous cell carcinoma in situ, seen as an erythematous plaque with overlying scale (hence
can be confused as discoid eczema, psoriasis or tinea)
o 5-10% risk of malignant transformation
o Usually found on lower limb with chronic exposure
Malignant lesions
• Basal cell carcinoma is the most common skin cancer and it develops from basal cells of
epidermis after chronic exposure (esp. the nose)
o Risks: Fair skin and immunosuppression
o Appearance:
§ Pearly surface with rolled edge
§ Telangiectasia
§ Ulceration (rodent ulcer)
o Additional types exist other than classic pearlescent nodule, such as morphoeic (scar-
like) and superficial (scab-like)
o Almost no risk of malignant change
Michael Grant
lOMoARcPSD|4927727

• Squamous cell carcinoma develops from keratinocytes producing a fleshy nodule
with a keratotic surface
o They grow rapidly, allowing them to be distinguished from BCC
o Risk factors:
§ Sun exposure +/- fair skin
§ Immunosuppression
§ Chronic inflammation (maljorin’s ulcer)
§ Metastasis risk
• Size and depth
• Location (increased risk at ear and lip)
• Immunosuppression
• Poorly differentiated
o Rx: Excision
• Malignant melanoma develops from melanocytes in the epidermis with sun binging and
may develop from a previous lentigo
o Prognosis is based on breslow’s depth:
§ <1mm - >95% 5YS
§ >3mm - <40% 5YS
o Risk factors:
§ Fair skin
§ Sun binging (with burns)
§ Male gender
§ FHx
§ Multiple moles (>50)
o Rx: Excision and advice:
§ Reduce high risk behaviours and follow up appointments
§ Family risk
• Mycosis fungoides is a T-Cell lymphoma of the skin that can
often mimick eczema
o The name mycosis fungoides is very misleading—it loosely
means "mushroom-like fungal disease". The disease,
however, is not a fungal infection but rather a type of non-
Hodgkin's lymphoma
o Often may be indolent, requiring only topical steroids and
UVB
o It can progress from patches/plaques to tumours stage with systemic
involvement
§ This requires chemo/radiotherapy
o Sezary syndrome is an aggressive systemic variety that produces
erythromderma and abnormal lymphocytes on blood film
Blistering disorder
• Bullous pemphigoid is the most common auto-immune blistering disorder,
commonly seen in the elderly population; thus it often occurs with co-morbidities
(esp. dementia, parkinson’s)
o Pathogenesis involves antibodies to the basement membrane zone (namely
to pemphigoid antigen 1 & 2), which can be seen as IgG and C3 on
immunofluorescence between the dermis and the epidermis
o May remit on it’s own
o Clinical features:
§ Itchy tense blister (look like they’re ready to pop)
§ Background of urticarial and eczematous skin change
§ 50% mucosal involvement with scarring
o Rx:
§ Mild-moderate: super potent topical steroids + tetracyclines
§ Moderate-severe: high dose prenisalone (co-prescribe bone and GI
protection as well as monitor BP & glucose)
§ Consider adding in steroid sparing agents (azathioprine)
• Pemphigus vulgaris is a rare condition that affects a younger age group and
has a high mortality if untreated
o Pathogenesis is the development of antibodies to the desmosomes found
in the epidermis; that can be seen as a “chicken wire” appearance of IgG &
C3 on immunofluorescence
§ This creates an intra-dermal blister that are very fragile and so rupture
leading to skin erosions
o Clinical signs:
§ Mucosal ulceration (can appear month before)
§ Itchy, painful, flaccid blisters
§ +ve Nikolski sign (used to differentiate from Bullous Pemphigoid)
Michael Grant
lOMoARcPSD|4927727

o Rx: Same as for bullous pemphigoid, but also consider rituximab
• Dermatitis herpetiformis is an immune blistering disorder seen in men with
coeliac disease
o Pathogenesis: IgA antibodies to tissue trans-glutaminase in the skin and gut –
seen on immunofluroesence as just below the BMZ
o Clinical features:
§ Intensely itchy rash made up of small tense blisters
§ Many erosions can be seen from scratching
§ Effects the extensor surfaces – scalp, buttocks, elbows and knees
• Can be mistaken for eczema
§ Investigations:
• Skin biopsies for anti-TTG IHC
• Blood tests for anti-TTG
§ Rx:
• Gluten free diet
• Consider topical steroids and dapsone
Michael Grant

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Medicine (Queen's University Belfast)

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General Medicine: Page 2 of 106

Pneumonia can be classified by

Lobar pneumonia is when an entire lobe is uniformly inflamed

General Medicine: Page 3 of 106

Complications of pneumonia include:

General Medicine: Page 4 of 106

General Medicine: Page 5 of 106

• Emergency management: give 10 puffs and if no improvement

General Medicine: Page 6 of 106

Tuberculosis is a chronic recurrent

Cystic fibrosis is one of the commonest life-threatening

General Medicine: Page 7 of 106

Lung fibrosis can be:

General Medicine: Page 8 of 106

General Medicine: Page 9 of 106

Extrinsic allergic alveolitis is effectively asthma of the alveolus due to an exposure

General Medicine: Page 10 of 106

Risk factors: Cigarette smoking is the major risk factor

General Medicine: Page 11 of 106

Secondary lung neoplasms can arise from different systems especially:

General Medicine: Page 12 of 106

General Medicine: Page 13 of 106

Bundle Branch Block:

General Medicine: Page 14 of 106

• Can be caused by Lyme disease and SLE

General Medicine: Page 15 of 106

Cardiovascular ischaemia and infarction

Vascular insufficiency causes can be considered as:

Thrombosis can be divided into:

Thrombi can meet a number of fates:

General Medicine: Page 16 of 106

Atheroma is the deposition of lipids in the

Ischaemic heart disease ranges from angina (stable or unstable), myocardial

General Medicine: Page 17 of 106

Acute coronary syndrome encompasses:

General Medicine: Page 18 of 106

Hypertension can be classified based on it’s aetiology, i.e. “primary”

General Medicine: Page 19 of 106

General Medicine: Page 20 of 106

General Medicine: Page 21 of 106

Acute AF (<48h) require treatment immediately:

General Medicine: Page 22 of 106

Valve disease typically can take one of 3 forms:

General Medicine: Page 23 of 106

Mitral stenosis is restricted almost exclusively to older patients as rheumatic fever

General Medicine: Page 24 of 106

Mitral regurgitation is much more common that

General Medicine: Page 25 of 106

Infective endocarditis occurs during endothelia injury healing, in which a

Risk factors: FROM JANE:

Diagnosis: (Duke’s criteria – box to right)

General Medicine: Page 26 of 106

Recommendations: Give clear information about prevention, including:

Hypertrophic cardiomyopathy is the presence of inappropriate ventricular

General Medicine: Page 27 of 106

Myocarditis is an inflammation of the myocardium of the heart.

Pericarditis is an inflammation involving the visceral and/or pariental pericardium –

Aneurysms are defined as “a localised, permanent, abnormal