• Definition: Fever ≥38°C and neutrophils <0.5 × 10⁹/L (or expected to fall)
• Common pathogens: Gram-negative bacilli (e.g., Pseudomonas),
Gram-positive cocci (e.g., coagulase-negative staph), Candida
• Initial management:
o Immediate empirical broad-spectrum IV antibiotics (do not wait for cultures)
o Example: piperacillin-tazobactam ± gentamicin
• Avoid:
o Rectal exams → mucosal injury → bacteraemia
o NSAIDs → mask fever, increase renal injury risk
• Causes: vertebral metastases (breast, prostate, lung, myeloma)
• Key features:
o Severe back pain, worse when lying flat or with Valsalva
o Motor weakness, sensory level
o Urinary retention or incontinence, faecal incontinence
• Urgent management:
o High-dose IV dexamethasone (e.g., 16 mg/day) → reduce oedema
o MRI entire spine urgently
o Definitive treatment: surgical decompression or radiotherapy depending on prognosis and tumour type
• Causes:
o Lung cancer (especially small cell)
o Non-Hodgkin lymphoma
o Thrombosis (e.g., catheter-related)
• Clinical features:
o Facial, periorbital and upper limb swelling
o Dyspnoea, cough, orthopnoea
o Distended neck and chest wall veins ("collaterals")
o Headache, dizziness (cerebral congestion)
• Investigations:
o CXR: widened mediastinum
o CT thorax with contrast: assess cause, extent
• Management:
o Elevate head, oxygen
o Dexamethasone to reduce tumour oedema
o Endovascular stenting if severe symptoms
o Definitive treatment: chemotherapy (SCLC) or radiotherapy
• At risk: high tumour burden, rapidly proliferating malignancies
o High-grade lymphomas (e.g., Burkitt)
o Acute leukaemias (especially ALL)
• Biochemical features:
o ↑ Potassium, ↑ phosphate, ↑ uric acid, ↓ calcium
• Complications:
o AKI (uric acid and calcium phosphate precipitation)
o Arrhythmias, seizures
• Prevention:
o Vigorous IV hydration
o Allopurinol (xanthine oxidase inhibitor) or rasburicase (urate oxidase; rapidly lowers uric acid)
• Treatment:
o Continue hydration
o Correct electrolytes
o Rasburicase if hyperuricaemia established
• Mechanisms:
o PTHrP secretion (squamous cell carcinoma)
o Bone metastases (breast, myeloma)
o Vitamin D production (lymphoma)
• Clinical features:
o Polyuria, polydipsia
o Dehydration, nausea
o Confusion, reduced consciousness
o Arrhythmias (short QT)
• Diagnosis: serum calcium >3.0 mmol/L often symptomatic
• Management:
o IV saline rehydration (restore volume, promote calciuresis)
o IV bisphosphonates (zoledronic acid or pamidronate)
o Consider calcitonin for rapid but temporary reduction
• Causes:
o Waldenström macroglobulinaemia (IgM)
o Multiple myeloma (high IgG or IgA)
• Clinical features:
o Visual disturbance ("sausage link" retinal veins)
o Headache, dizziness
o Bleeding diathesis (impaired platelet function)
• Treatment: plasmapheresis
• Causes:
o Small cell lung cancer (ectopic ADH)
o CNS disease (e.g., stroke, trauma, infection)
o Drugs: SSRIs, carbamazepine, cyclophosphamide
• Features:
o Euvolaemic hyponatraemia
o Confusion, seizures if severe
• MEN 1 ("3 Ps"): pituitary, parathyroid, pancreatic tumours
• MEN 2A: medullary thyroid carcinoma, phaeochromocytoma, hyperparathyroidism
• MEN 2B: medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas, marfanoid habitus
• Screening and prophylactic thyroidectomy often required in RET mutations
• TLS → always check baseline uric acid and renal function before induction chemotherapy
• Bone metastases (breast, prostate) → bisphosphonates also help reduce skeletal events
• Hypercalcaemia → "stones, bones, groans, thrones, psychiatric overtones"
————————————————————————————————————————————————————————————————————————————————————————————————————————-
Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
