Differentials
Common
Hypotonic replacement of excess fluid loss
History
history of excessive sweating, vomiting, diarrhoea, GI fistulas or drainage tubes, or third spacing of fluids (peritonitis, pancreatitis, burns, small bowel obstruction) and fluid replacement by tap water or hypotonic intravenous fluids
Exam
clinical signs of volume depletion: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure; small bowel obstruction: abdominal distension; peritonitis: rebound abdominal tenderness; cutaneous burns
1st investigation
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
Drug-induced
History
history of use of antidepressants (e.g., selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, venlafaxine), thiazide diuretics, anti-epileptics (e.g., carbamazepine, sodium valproate, lamotrigine), vasopressin analogues (desmopressin, oxytocin), non-steroidal anti-inflammatory drugs, opiates, nicotine, chlorpropamide, vincristine, cyclophosphamide, clofibrate, mannitol
Exam
usually normal
1st investigation
- trial of discontinuation of causative medication:
hyponatraemia resolves
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O) or >295 mmol/kg H₂O (>295 mOsm/kg H₂O) with mannitol
- urine sodium level:
>20 mmol/L (>20 mEq/L)
Other investigations
- serum osmolar gap:
>10 mmol/kg H₂O (>10 mOsm/kg H₂O) with mannitol
Chronic kidney disease
History
known diagnosis of chronic kidney disease, dialysis patients
Exam
bilateral oedema; may have associated ascites or pulmonary rales; hypertension may be seen; elevated jugular venous pressure from total body fluid overload
1st investigation
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- serum creatinine:
elevated
- urinalysis:
haematuria and/or proteinuria
Other investigations
- renal ultrasound:
small kidney size; presence of obstruction/hydronephrosis; kidney stones
- estimation of GFR:
reduced GFR
- kidney biopsy:
identification of underlying kidney pathology
Acute kidney injury
History
history of ≥1 of chronic kidney disease, heart failure, liver disease, diabetes, dementia; previous acute kidney disease (AKI) episode; exposure to nephrotoxic medicines (e.g., NSAIDs, diuretics, aminoglycoside anitbiotics; ACE inhibitors); symptoms or history of urological obstruction; suspected or confirmed sepsis. Increased risk in people aged ≥65 years
Exam
can range from non-specific findings to hypotension (systolic blood pressure <90 mmHg or a fall of >40 mmHg from baseline BP), multi-system failure, altered mental status, and muscle trauma. Oliguria (urine output <0.5 mL/kg/hour)
1st investigation
Other investigations
Congestive heart failure
History
fatigue, decreased exercise tolerance, dyspnoea on exertion, orthopnoea, paroxysmal nocturnal dyspnoea, previous myocardial infarction
Exam
oedema, displaced cardiac apex, hepatojugular reflux, jugular venous distension, S3 gallop, pulmonary rales, hepatomegaly
1st investigation
- natriuretic peptide biomarkers (B-type and N-terminal pro-B-type):
Elevated
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- chest x-ray:
cardiomegaly, pulmonary oedema, pleural effusion
- ECG:
anterior Q waves, bundle branch block, atrial arrhythmias, ventricular arrhythmias, left axis deviation, ventricular hypertrophy
Other investigations
- echocardiogram:
systolic and diastolic dysfunction, valve lesions, signs of pericardial injury or cardiomyopathy
Cirrhosis
History
history of alcohol misuse, intravenous drug use, unprotected intercourse, obesity, blood transfusion, known hepatitis infection; fatigue, weakness, weight loss, or pruritus
Exam
oedema, jaundice, ascites, collateral circulation, hepatosplenomegaly, leukonychia, palmar erythema, spider angiomata, telangiectasia, jaundiced sclera, hepatic fetor, altered mental status
1st investigation
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- serum ALT and AST:
elevated with ALT:AST ratio ≥1 if hepatocellular damage; normal in cholestasis
- bilirubin:
normal in compensated cirrhosis; elevated in decompensated cirrhosis
- serum albumin:
decreased
- PT or INR:
increased
- platelet count:
decreased
Other investigations
- serum alkaline phosphatase and gamma-GT:
elevated in cholestasis
- abdominal ultrasound:
liver surface nodularity, small liver, possible hypertrophy of left/caudate lobe, ascites, splenomegaly, increased diameter of the portal vein (≥13 mm) or collateral vessels
- liver biopsy:
architectural distortion of the liver parenchyma with formation of regenerative nodules
Hyperglycaemia
History
diabetes: history of diabetes, poor diabetes control, obesity, polyuria, polydipsia, blurred vision; use of causative medications: corticosteroids, nicotinic acid, pentamidine, protease inhibitors, some antipsychotics; stress hyperglycaemia: recent stroke, myocardial infarction, trauma, infection, inflammation
Exam
features of metabolic syndrome in type 2 diabetes
1st investigation
- serum osmolar gap:
>10 mmol/kg H₂O (>10 mOsm/kg H₂O)
- serum osmolality:
>295 mmol/kg H₂O (>295 mOsm/kg H₂O)
- fasting plasma glucose:
>6.9 mmol/L (>125 mg/dL)
- random plasma glucose:
>8.3 mmol/L (>150 mg/dL)
- trial of discontinuation of causative medication:
resolution of hyponatraemia and hyperglycaemia
Other investigations
- HbA1c:
elevated in diabetes
Psychogenic polydipsia
History
history of schizophrenia or psychotic depression; phenothiazine medications; polydipsia; polyuria
Exam
usually normal; weight gain due to high water intake may occur in extreme cases
1st investigation
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
Other investigations
- urine osmolality:
<100 mmol/kg H₂O (<100 mOsm/kg H₂O)
Intracranial surgery
History
history of recent intracranial surgery
Exam
signs of volume depletion in cerebral salt-wasting syndrome: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- urine osmolality:
low or normal in cerebral salt-wasting syndrome; high in SIADH
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
Other investigations
- CT head:
exclude intracranial haemorrhage
Head injury
History
history of head trauma, possible loss of consciousness
Exam
may be normal in minor injuries; bruising or lacerations of scalp; evidence of basilar skull fracture: blood in the middle ear cavity (haemotympanum), peri-orbital ecchymosis (panda eyes), post-auricular ecchymosis, CSF leakage (rhinorrhoea or otorrhoea); papilloedema, retinal haemorrhage; decreased conscious level; signs of volume depletion in cerebral salt-wasting syndrome: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- urine osmolality:
low or normal in cerebral salt-wasting syndrome; high in SIADH
Other investigations
- CT head:
will show skull fracture, contusions, or haemorrhage
More
Small cell lung cancer (SCLC)
History
history of cigarette smoking or exposure to tobacco smoke, radon gas, or asbestos; cough, haemoptysis, chest pain, dyspnoea, weight loss, fatigue
Exam
patient may appear unwell with dyspnoea and cachexia, finger clubbing, hypertrophic osteoarthropathy, and dullness to percussion of the lung fields
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- chest x-ray:
central mass, hilar lymphadenopathy, pleural effusion
- CT chest, liver, and adrenal glands:
massive lymphadenopathy and direct mediastinal invasion are common features of SCLC; determines extent of disease
- sputum cytology:
malignant cells in sputum
Other investigations
- bronchoscopy + biopsy or transbronchial needle aspiration biopsy:
malignant cells, high nuclear-to-cytoplasmic ratio, nuclear fragmentation often present
Irrigation of operative field
History
irrigation of operative field with hypertonic fluids during transurethral resection of prostate or hysteroscopy, or with hypotonic fluids during endometrial ablation
Exam
normal
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O) or >295 mmol/kg (>295 mOsm/kg H₂O) if hyperosmolar solute absorbed
Other investigations
Artifact in multiple myeloma
History
positive family history, previous exposure to irradiation or petroleum products, known abnormal free light-chain ratio; fatigue, pallor, shortness of breath, bone pain usually localised to the back
Exam
usually normal
1st investigation
- urine sodium level:
10-20 mmol/L (10-20 mEq/L)
- serum osmolality:
275-295 mmol/kg H₂O (275-295 mOsm/kg H₂O)
- urine sodium level using direct ion-sensitive electrode:
normal sodium concentration
Other investigations
- serum or urine electrophoresis:
paraprotein spike (IgG >35 g/L [>3500 mg/dL] or IgA >20000 mg/L [>200 mg/dL] and light-chain urinary excretion >1 g/day); hypogammaglobulinaemia
Uncommon
Potomania
History
drinking >6 litres of beer a day with poor dietary intake; CAGE score >2; inadequate diets (i.e., very low-calorie diets with high fluid intake), or crash diets
Exam
signs of alcoholic liver disease may be present: jaundice, parotid gland enlargement, Dupuytren's contracture, generalised wasting, ecchymosis or petechiae, spider angioma, thenar eminence loss, palmar erythema, caput medusa, ascites, hepatosplenomegaly, or small liver
1st investigation
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- urine osmolality:
<100 mmol/kg H₂O (<100 mOsm/kg H₂O)
Other investigations
- serum LFTs:
high direct bilirubin; AST and ALT rarely >200 units/L
Nephrotic syndrome
History
history of long-standing diabetes, malignancy, systemic lupus erythematosus, HIV infection, multiple myeloma, connective tissue diseases, or amyloidosis; use of known causative medications (pamidronate, lithium, gold, penicillamine, or NSAIDs, and, very rarely, interferon alfa, heroin, mercury, or formaldehyde); foamy urine
Exam
oedema of legs or whole body, Muehrcke's lines, xanthelasmas
1st investigation
- urine sodium level:
≤20 mmol/L (≤20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- serum albumin:
decreased
- serum creatinine:
normal or elevated
- 24-hour urine collection for protein:
>3 g/24 hours proteinuria
- trial of discontinuation of causative medications:
resolution of symptoms
Other investigations
- HbA1c:
elevated in diabetes
- HIV test:
positive in HIV-induced focal segmental glomerulosclerosis
- renal biopsy:
identifies underlying cause of nephrotic syndrome
Salt-wasting nephropathy
History
history of tubulointerstitial disease (interstitial nephritis, medullary cystic kidney disease, partial urinary tract obstruction, and polycystic kidney disease); positive family history of medullary cystic disease
Exam
clinical signs of volume depletion: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure; abdominal mass in polycystic kidney disease; pallor due to anaemia in medullary cystic kidney disease
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- serum creatinine:
normal or elevated
- renal ultrasound:
presence of obstruction/hydronephrosis; kidney stones; cysts in polycystic kidney disease
- FBC:
severe normocytic normochromic anaemia in medullary cystic disease
Other investigations
- contrast-enhanced abdominal CT scan:
identification of renal cysts in polycystic kidney disease or medullary/corticomedullary cysts in medullary cystic disease
- estimation of GFR:
normal or reduced GFR
- kidney biopsy:
identification of interstitial nephritis
- genetic testing:
causative mutations of polycystic kidney disease or medullary cystic kidney disease
Mineralocorticoid deficiency
History
weakness, fatigue, nausea, vomiting, myalgia, and arthralgia
Exam
clinical signs of volume depletion: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure; adrenal crisis: postural hypotension, hypovolaemic shock
1st investigation
- serum potassium:
elevated
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- morning serum cortisol:
decreased
Other investigations
- ACTH stimulation test:
cortisol levels <496.6 nanomol/L (<18 micrograms/dL) 30 and/or 60 minutes after 250 micrograms intravenous/intramuscular ACTH
Idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH)
History
diagnosis of exclusion in a patient with euvolaemic hyponatraemia
Exam
usually normal; may have signs of cerebral oedema: nausea, vomiting, altered mental status, headache, seizure, coma
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
Other investigations
Stroke
History
weakness, vision loss, aphasia, high urine output in cerebral salt-wasting syndrome, low urine output in SIADH
Exam
ataxia, visual-field defect, unilateral sensory impairment, or motor weakness; signs of volume depletion in cerebral salt-wasting syndrome: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- urine osmolality:
low or normal in cerebral salt-wasting syndrome; high in SIADH
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- head CT scan:
haemorrhagic stroke: enhancing lesion; ischaemic stroke: hypoattenuation (darkness) of the brain parenchyma; loss of gray-white matter differentiation, and sulcal effacement; hyperattenuation (brightness) in an artery indicates clot within the vessel lumen
More - head MRI scan:
ischaemic stroke: acute ischaemic infarct appears bright on diffusion-weighted imaging; at later stages, T2 images may also show increased signal in the ischaemic territory
Other investigations
Subarachnoid haemorrhage
History
sudden, severe occipital headache; nausea and vomiting; photophobia
Exam
decreased conscious level, intra-ocular haemorrhage; signs of volume depletion in cerebral salt-wasting syndrome: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- urine osmolality:
low or normal in cerebral salt-wasting syndrome; high in SIADH
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- CT head:
hyperdense areas in the basal cisterns, major fissures, and sulci
Other investigations
- lumbar puncture:
bloody CSF (xanthochromia)
Meningitis
History
headache, neck stiffness, photophobia
Exam
haemorrhagic rash, Kernig's sign
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- lumbar puncture:
elevated white cell count, identification of causative organism
Other investigations
Brain abscess
History
history of sinusitis, otitis media, recent dental procedure or infection, recent neurosurgery, meningismus, headache
Exam
fever, positive Kernig's sign, III or VI cranial nerve palsy, papilloedema, focal neurological signs; infants: increased head circumference, bulging fontanelle
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- FBC:
leukocytosis
- serum erythrocyte sedimentation rate (ESR):
elevated
- head MRI with contrast:
one or more ring-enhancing lesions
Other investigations
Lymphoma
History
fever, chills, night sweats, pruritus, weight loss, lymphadenopathy
Exam
fever, lymphadenopathy, splenomegaly
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- lymph node biopsy:
Reed-Sternberg cells with expression of CD15 and CD30 in Hodgkin's lymphoma; immunohistochemistry and flow cytometry identify the subtype of non-Hodgkin's lymphoma
Other investigations
Cervical cancer
History
early stage is asymptomatic; pre-invasive lesions found after abnormal routine-screening Pap smear; pelvic pain, dyspareunia, post-coital bleeding, mucoid or purulent vaginal discharge, abnormal vaginal bleeding
Exam
cervical mass, cervical bleeding
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- colposcopy:
abnormal vascularity, white change with acetic acid or obvious exophytic lesions
- biopsy:
abnormal
Other investigations
- HPV testing:
positive or negative
Leukaemia
History
fevers, night sweats, lymphadenopathy, fatigue, weakness, early satiety
Exam
fever, lymphadenopathy, splenomegaly
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- FBC with differential and review of the peripheral smear:
elevated WBC, anaemia, thrombocytosis; characteristic appearance of CLL cells: mature-appearing lymphocytes with dense chromatin
- peripheral blood smear:
myeloid maturing cells, elevated basophils and eosinophils
- bone marrow biopsy:
granulocytic hyperplasia in CML
- peripheral blood flow cytometry:
positive for CD19, CD20 (usually weak), CD21, CD23, CD24, CD5; negative for cyclin D1, CD10, CD22, CD79b in CLL
Other investigations
Central nervous system tumours
History
symptoms of raised intracranial pressure: headache, altered mental status, nausea and/or vomiting and gait abnormality, cranial nerve palsy, hearing loss
Exam
astrocytic brain tumours: focal neurological signs; craniopharyngioma: visual field defects, growth retardation; signs of volume depletion in cerebral salt-wasting syndrome: decreased skin turgor, reduced jugular venous pressure, decreased blood pressure
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- urine osmolality:
low or normal in cerebral salt-wasting syndrome; high in SIADH
- MRI head:
identification of brain tumour
Other investigations
- histology of biopsy or resected tumour:
identification of tumour type
More
Pancreatic cancer
History
anorexia, malaise, nausea, fatigue, mid-epigastric or back pain
Exam
significant weight loss, jaundice
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- CT abdomen:
identification of tumour
Other investigations
- carbohydrate antigen 19-9:
elevated
Pneumonia
History
cough, shortness of breath, pleuritic chest pain
Exam
bronchial breath sounds, crepitations
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- FBC:
leukocytosis
- chest x-ray:
unilateral infiltration, consolidation, effusions, cavitation
- sputum cultures:
identification of causative organism
Other investigations
- blood cultures:
identification of causative organism
More
Lung abscess
History
fever; cough with foul-smelling, bad-tasting sputum production; night sweats, anorexia, weight loss, pleuritic chest pain, haemoptysis
Exam
low-grade fever in anaerobic infections or high-grade fever in other infections; gingival disease, decreased breath sounds, dullness to percussion, bronchial breath sounds, crepitations, finger clubbing
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- FBC:
leukocytosis
- sputum Gram stain and cultures:
identification of causative organism
- blood cultures:
identification of causative organism
- chest x-ray:
irregular shaped cavitation with an air-fluid level
Other investigations
- chest CT:
radiolucent thick-walled parenchymal lesion with ill-defined irregular margins; no displacement of blood vessels or bronchi
COPD
History
history of smoking or exposure to dust, traffic exhaust fumes, or sulphur dioxide; productive cough, wheezing, shortness of breath on exertion
Exam
tachypnoea, respiratory distress, use of accessory muscles, intercostal retraction, barrel chest, clubbing, cyanosis; hyper-resonance on percussion; wheezing, distant breath sounds, and/or poor air entry on auscultation
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- spirometry:
FEV1/FVC ratio <70% with no evidence of reversibility with bronchodilator
Other investigations
- pulse oximetry:
low oxygen saturation
- chest x-ray:
hyperinflation
More
Cystic fibrosis
History
positive family history, detection during antenatal screening; chronic or recurrent cough, recurrent respiratory infections, shortness of breath on exertion, steatorrhoea, infertility
Exam
tachypnoea, respiratory distress, use of accessory muscles, intercostal retraction, barrel chest, clubbing, cyanosis; hyper-resonance on percussion; abdominal distension, hepatosplenomegaly, rectal prolapse; signs of fat-soluble vitamin deficiencies (A,D,E, or K); scoliosis, kyphosis
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
- sweat test:
elevated chloride level
- chest x-ray:
hyperinflation, peri-bronchial thickening, air trapping with bronchiectasis in upper lobes; pulmonary nodules, flattened diaphragmatic domes, thoracic kyphosis, and bowing of the sternum appear as disease advances
Other investigations
- pulmonary function tests:
normal FEV1 with reduced FEF 25% to 75% and increased residual volume: total lung capacity ratio; FEV1 falls as disease progresses
- genotyping:
identification of mutations in CFTR
Positive-pressure ventilation
History
history of endotracheal intubation and ventilation to maintain respiratory function in respiratory failure, acute or impending respiratory arrest, respiratory distress syndrome, respiratory muscle fatigue, neuromuscular disease, severe trauma, or coma
Exam
signs of the underlying cause; patient is intubated in an ICU setting
1st investigation
- urine sodium level:
>20 mmol/L (>20 mEq/L)
- serum osmolality:
<275 mmol/kg H₂O (<275 mOsm/kg H₂O)
Other investigations
Artifact in hypertriglyceridaemia
History
usually asymptomatic (pseudohyponatraemia); may present with hypertriglyceridaemia-induced acute pancreatitis
Exam
possible eruptive xanthoma; may have signs of acute pancreatitis (e.g., upper abdominal pain, nausea and vomiting, hypovolaemia)
1st investigation
- urine sodium level:
10-20 mmol/L (10-20 mEq/L)
- serum osmolality:
275-295 mmol/kg H₂O (275-295 mOsm/kg H₂O)
- serum lipid profile:
markedly elevated triglycerides; highly elevated cholesterol and LDL
- urine sodium level using direct ion-sensitive electrode:
normal sodium concentration
Other investigations
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