Biochemical DDx Flashcards
normal level of urea
2.5–6.6 mmol/L
INCREASED BUN
• Renal failure (acute and chronic) • Dehydration • Shock • Congestive cardiac failure • Gastrointestinal haemorrhage (digested blood increases blood urea) • Excessive protein intake • Excessive protein catabolism
DECREASED BUN
- Malnutrition
- Liver failure
- Overhydration, e.g. prolonged i.v. fluids
- Pregnancy (increased plasma volume)
- Impaired protein absorption
- SIADH
- Anabolic steroid use
BUN Sx
Signs of uraemia, e.g. oliguria, anuria, fatigue, confusion, thirst,
bronze colour of skin, oedema (peripheral and pulmonary), uraemic
frost (rare).
Signs of dehydration, e.g. dry skin, loss of skin turgor.
Signs of congestive cardiac failure, e.g. oedema, JVP . GI
haemorrhage, e.g. tachycardia, hypotension, haematemesis and
melaena. Decreased intake, e.g. oedema, ascites.
Signs of liver failure. SIADH, e.g. head injury, small cell lung
cancer.
BUN Dx
INVESTIGATIONS ■■ UEs ■■ Creatinine ■■ FBC ■■ LFTs ■■ MSU ■■ CXR ■■ Urine electrolytes ■■ Urine osmolality ■■ US ■■ MAG 3 scan
A grossly raised BUN in association with metabolic
acidosis, hyperkalaemia, fluid overload and clinical
symptoms, e.g. coma, pericarditis, is an indication for
urgent haemodialysis
Hypercalcaemia is above
2.62 mmol/L
Sx @ 3.5
Hypercalcaemia CAUSES
• Malignancy
• Solid tumour with lytic bony metastases, e.g. Ca breast,
bronchus
• Solid tumours with humoral mediation, e.g. inappropriate
PTH secretion with carcinoma of the bronchus, carcinoma
of the kidney
• Multiple myeloma
• Hyperparathyroidism (primary, secondary, tertiary)
• Sarcoidosis
• Drugs, e.g. thiazide diuretics, lithium
• Excess intake of vitamin A, vitamin D or calcium
• Prolonged immobilisation
• Milk-alkali syndrome (excess calcium intake)
• Hyperthyroidism
• Addison’s disease
• Paget’s disease of bone
• Familial hypocalciuric hypercalcaemia
hypercalcaemia Sx
nausea and vomiting, fatigue,
depression, confusion, psychosis; abdominal pain, constipation,
acute pancreatitis, peptic ulceration, polyuria/nocturia, haematuria,
renal colic, renal failure, bone pain, hypertension and arrhythmias.
hypercalcaemia +
hyperparathyroidism Sx
stones, bones, abdominal groans and
psychiatric overtones
hypercalcaemia Dx
■■ Fasting calcium and phosphate Ca increased PO4 decreased. ■■ U&Es I creatinine I urea. Renal failure ■■ PTH levels I hyperparathyroidism. ■■ Protein electrophoresis and Bence Jones protein Multiple myeloma. ■■ ECG Short QT interval. Widened T waves. ■■ Serum amylase I in acute pancreatitis associated with hyperparathyroidism. ■■ AXR Stones. Nephrocalcinosis. ■■ US Renal stones. Carcinoma of the kidney (inappropriate PTH secretion). Parathyroid lesions. ■■ Skull X-ray Myeloma. Abnormal sella turcica in MEN associated pituitary tumour. Paget’s disease of bone. ■■ Sestamibi scan Hyperparathyroidism. ■■ 24-hour urinary calcium excretion calcium excretion in hyperparathyroidism (calcium-restricted diets).
with depression or psychosis OR presenting with polyuria, if diabetes has been excluded always check the
serum calcium. Hyperparathyroidism may
be a cause.
Hyperglycaemia
plasma glucose >7.0 mmol/L
Hyperglycaemia causes
ENDOCRINE • Diabetes mellitus (types 1 and 2) SYSTEMIC DISEASE • Cushing’s syndrome SEVERE STRESS • Stroke • Myocardial infarction PSYCHOGENIC • Bulimia nervosa PHYSIOLOGICAL • Infection • Inflammation OTHER • Pregnancy
DRUGS causing Hyperglycaemia
- Corticosteroids
- Beta blockers
- Thiazide diuretics
- Niacin
- Pentamidine
- Protease inhibitors
- l-asparaginase
- Antipsychotic agents
Hyperglycaemia Sx
polydipsia, polyuria,
polyphagia, fatigue, weight loss and blurred vision
Acute DKA
hyperventilation, stupor or coma
Recurrent infections
Hyperglycaemia
INVESTIGATIONS
■■ BM stix ■■ Blood glucose ■■ Urinalysis ■■ Oral glucose tolerance test ■■ U&Es ■■ FBC ■■ bHCG ■■ HbA1c ■■ ABGs
Hyperkalaemia is above
5.0 mmol/L
Hyperkalaemia CAUSES
• Excess administration of potassium, especially rapidly
• Renal failure
• Haemolysis
• Massive blood transfusion
• Crush injuries (rhabdomyolysis)
• Tissue necrosis, e.g. burns, ischaemia
• Metabolic acidosis
• Adrenal insufficiency (Addison’s disease)
• Drugs interfering with urinary excretion: ACE inhibitors
and angiotensin receptor blockers, potassium-sparing
diuretics (spironolactone and amiloride), NSAIDs (ibuprofen,
naproxen), calcineurin inhibitors for immunosuppression
(ciclosporin and tacrolimus), trimethoprim, pentamidine
Hyperkalaemia Sx
Cardiac arrest
Mild breathlessness (hyperkalaemia associated with
metabolic acidosis). Paraesthesiae, areflexia. Weakness.
Palpitations.
Abdominal pain. Hypoglycaemia. Hyperpigmentation associated with Addison’s disease.
Hyperkalaemia Dx
U+Es FBC ABGs Blood Glucose ECG Cr Plasma cortisol
Hypokalaemia =
3.5 mmol/L
Hypokalaemia two big causes
INADEQUATE INTAKE
• Potassium-free i.v. fluids
• Reduced oral intake, e.g. coma, dysphagia
EXCESSIVE LOSS Renal • Diuretics • Renal tubular disorders Gastrointestinal • Diarrhoea • Vomiting • Fistulas • Laxatives • Villous adenoma Endocrine • Cushing’s syndrome • Steroid therapy • Hyperaldosteronism
Hypokalaemia Sx
Muscle weakness. Myalgia. Constipation. Paralytic ileus. Cardiac arrhythmia (ranging from ectopics to serious arrhythmias with
sudden death at very low levels of potassium)
Hypokalaemia Dx
U+Es ABG ECG Flattened T waves. ST depression. U waves. Prolonged QT intervals. Serum Mg Plasma aldosterone, renin, cortisol urinary free cortisol ACTH levels
• In a patient with prolonged ileus post-operatively
or
In a patient presenting with unexplained lethargy,
fatigue and muscle weakness
serum potassium
normal serum sodium level
Hypernatraemia
135–145 mmol/L
> 145 mmol/L.
Hypernatraemia CAUSES
DECREASED WATER INTAKE
NON-RENAL WATER LOSSES
RENAL WATER LOSSES
SODIUM EXCESS
Hypernatraemia CAUSES
DECREASED WATER INTAKE
- Confusion
* Coma
Hypernatraemia CAUSES
NON-RENAL WATER LOSSES
- Gastrointestinal losses (e.g. vomiting, diarrhoea)
- Pyrexia
- Burns
Hypernatraemia CAUSES
RENAL WATER LOSSES
- Osmotic diuresis
- Hyperglycaemia
- Nephrogenic diabetes insipidus
- Drugs (e.g. lithium)
- Bence Jones proteins
- Post-relief of obstructive uropathy
- Recovering acute tubular necrosis
- Congenital diabetes insipidus
Hypernatraemia CAUSES
SODIUM EXCESS
- Excessive intravenous sodium therapy
- Chronic congestive cardiac failure
- Cirrhosis of the liver
- Steroid therapy
- Cushing’s syndrome
- Primary hyperaldosteronism (Conn’s syndrome)
Hypernatraemia Sx
Thirst 3–4 mmol/L
above upper limit of normal
coma, seizures, muscular tremor and rigidity above
158 mmol/L.
Hypernatraemia Dx
■■ U&Es
Na+ 150–170 mEq/L usually indicates dehydration. Na+ >170 mEq/L
usually indicates diabetes insipidus. Na+ >190 mEq/L usually
indicates long-term salt ingestion.
■■ Urine osmolality
Central versus nephrogenic diabetes insipidus.
■■ CT head
Central diabetes insipidus, e.g. cerebral tumour/trauma.
BEWARE in Hypernatraemia
Rapid correction of hypernatraemia can lead to
cerebral oedema.
Lack of thirst is associated with CNS disease.
normal serum sodium level
Hyponatraemia
Severe hyponatremia
135–145 mmol/L
less than 135 mmol/L
less than 120 mmol/L
Hyponatraemia 3 types of causes
hypovolemic
euvolemic
oedematous
Hyponatraemia hypovolemic causes
Gastrointestinal losses • Diarrhoea • Vomiting • Fistula • Small bowel obstruction • Paralytic ileus
Renal sodium losses
• Diuretics
• Osmotic diuresis (e.g. hyperglycaemia)
• Renal failure
Other sodium losses • Burns • Ascites • Crush injuries • Peritonitis
Hyponatraemia euvolemic causes
Endocrine
• Severe hypothyroidism
• Addison’s disease
Water load
• Intravenous infusions
• Water drinking
• TURP (transurethral resection of prostate) syndrome
SIADH
• Pulmonary disease (e.g. pneumonia, lung cancer)
• Drugs (e.g. carbamazepine)
• Intracranial disease (e.g. tumour, head injuries)
Hyponatraemia oedematous causes
- Cardiac failure
* Nephrotic syndrome
Hyponatraemia Sx
asymptomatic mild nausea vomiting headache malaise diminished reflexes seizures stupor coma
Hyponatraemia Dx
U+Es
Paired serum and urine osmolality
Paired serum and urinary sodium
SIADH is suggested by
inappropriately concentrated urine (>100 mOsm/kg)
serum hypo-osmolality (<270 mOsm/kg).
inappropriately concentrated urinary sodium (>20 mmol/L).
Hyponatraemia BEWARE
Falsely low sodium values can occur with high
circulating levels of lipids, proteins and in severe
hyperglycaemia.
Most patients with hyponatraemia do not require
treatment with intravenous sodium chloride, but,
if this is required, the rate of correction of serum
sodium levels must be carried out with great care to
minimise the risk of central pontine demyelination.
Hypoglycaemia plasma glucose
<2.5 mmol/L
Hypoglycaemia CAUSES
DRUGS • Insulin • Sulfonylurea • Alcohol • Aminoglutethimide • Quinolones • Pentamidine • Quinine
ENDOCRINE
• Pituitary insufficiency
• Addison’s disease
NEOPLASTIC
• Pancreatic islet cell tumours; insulinoma
• Non-pancreatic tumours; retroperitoneal fibrosarcoma,
haemangiopericytoma
LIVER DISEASE • Inherited glycogen storage disorders • Cirrhosis • Acute liver failure • Alcohol
OTHER
• Post-prandial dumping syndrome (post-gastrectomy, postvagotomy
and drainage)
• Immune mediated (e.g. anti-insulin receptor antibodies in
Hodgkin’s disease)
Hypoglycaemia Sx
sweatiness palpitations weakness hunger drowsiness restlessness tremor seizures coma personality changes
Diagnosis of insulinoma
Whipple’s triad: (1) attacks precipitated by fasting (2) blood sugar is low during the attack (3) symptoms are relieved by administration of glucose
Hypoglycaemia
BM stix BG LFTs Tox screen U+Es Insulin + C peptide levels Pituitary hormone levels Prolonged oral glucose tolerance test IV Insulin suppression test Arterial stimulation with venous sampling CT MRI
Hypocalcaemia =
serum calcium of <2.0 mmol/L ionised fraction <0.8 mmol/L.
Hypocalcaemia CAUSES
ASSOCIATED WITH HIGH SERUM PHOSPHATE • Renal failure • Hypoparathyroidism • Rhabdomyolysis • Phosphate therapy
ASSOCIATED WITH LOW OR NORMAL SERUM PHOSPHATE
• Hypomagnesaemia
• Acute pancreatitis
• Critical illness including sepsis, burns
• Osteomalacia
• Overhydration
MASSIVE BLOOD TRANSFUSION DUE TO CITRATE-BINDING
HYPERVENTILATION WITH RESPIRATORY ALKALOSIS AND
REDUCTION IN IONISED PLASMA CALCIUM
DRUGS
• Bisphosphonates
• Calcitonin
Hypocalcaemia Sx
Circumoral paraesthesia
peripheral tingling and paraesthesia
cramp
tetany (carpo-pedal spasm) hypotension
hyperactive
tendon reflexes
Chvostek’s sign (tapping over the facial nerve causes facial spasm)
Trousseau’s sign (inflating blood pressure cuff
to above systolic pressure causes carpal spasm), laryngospasm (lifethreatening),
cardiac arrhythmias
dystonia and psychosis
Hypocalcaemia Dx
Serum Ca P U+E ABG Serum amylase Serum Mg PTH Serum Vit D ECG
The first symptom of hypocalcaemia is
circumoral paraesthesia
If this occurs after thyroid or
parathyroid surgery, it is an indication for an
urgent check of the serum calcium and appropriate
treatment.
normal range of serum magnesium
Hypomagnesaemia
serum level below
- 7–1.0 mmol/L
0. 7 mmol/L
Hypomagnesaemia CAUSES
EXCESSIVE LOSSES
or
INADEQUATE INTAKE
EXCESSIVE LOSSES • Diuretics • Severe diarrhoea • Prolonged vomiting • Polyuria (poorly controlled diabetes) • Prolonged and excessive nasogastric aspiration
INADEQUATE INTAKE • Starvation • Alcoholism • Malabsorption syndrome • Parenteral nutrition
Hypomagnesaemia Sx
muscle weakness lethargy irritability confusion seizures arrhythmias
Hypomagnesaemia Dx
Serum magnesium
U+Es
Serum Ca
If symptoms related to hypocalcaemia and
hypokalaemia are resistant to calcium and potassium
supplements, respectively, remember to check
serum magnesium level
Metabolic acidosis is caused by increased production of hydrogen ions from metabolic causes or from excessive bicarbonate loss (pH decreased, HCO3- decreased)
Compensatory mechanisms are
- decreased pCO2 by hyperventilation
* decreased H+ by kidneys (unless in renal failure)
Metabolic acidosis causes
EXCESSIVE PRODUCTION OF H+ • Diabetic ketoacidosis • Lactic acidosis secondary to hypoxia, e.g. shock, ischaemic gut • Septicaemia • Starvation • Drugs, e.g. ethanol, salicylates
DECREASED H+ EXCRETION
• Renal failure
EXCESSIVE LOSS OF BASE
• Diarrhoea
• Fistula – pancreatic, intestinal or biliary
EXCESSIVE INTAKE OF ACID
• Parenteral nutrition
Metabolic acidosis Sx
chest pain palpitations headache nausea vomiting abdominal pain weight loss Kussmaul respirations DKA
Extreme acidosis lethargy stupor coma seizures arrhythmias ventricular tachycardia
Metabolic acidosis Dx
ABGs FBC U+Es BG Serum salicylate
Anion gap = ( [Na+] + [K+] ) – ( [Cl–] + [HCO–3] )
normally about 8–16 mmol/L.
Increased anion gap >16 mmol/L causes
■■ Lactic acidosis. ■■ Ketoacidosis. ■■ Chronic renal failure. ■■ Intoxication, e.g. salicylate, ethanol, ethylene glycol, metformin. ■■ Massive rhabdomyolysis
Rapidly increasing metabolic acidosis over minutes
or hours is not due to renal failure.
Severe sepsis
tissue hypoperfusion
tissue necrosis
Rapidly increasing metabolic acidosis over minutes
or hours is not due to renal failure.
Severe sepsis
tissue hypoperfusion
tissue necrosis
Metabolic alkalosis is caused by an increase in HCO–
3 or decrease in
H+ (increased pH, increased HCO–3).
Compensatory mechanisms are:
• increased pCO2 by hypoventilation (limited by hypoxia)
• decreased HCO–
3 by kidneys.
Metabolic Alkalosis causes
EXCESS LOSS OF H+ • Vomiting • Nasogastric aspiration • Gastric fistula • Diuretic therapy (thiazide or loop) • Cushing’s syndrome (mineralocorticoid effect) • Conn’s syndrome (mineralocorticoid excess) EXCESSIVE INTAKE OF BASE • Antacids, e.g. milk-alkali syndrome • Ingestion of HCO– 3 (usually iatrogenic)
Metabolic Alkalosis Sx
ASx
hypoventilate
Metabolic Alkalosis Dx
blood gases
U+Es
Plasma cortisol
Plasma aldosterone
Metabolic alkalosis will cause a left shift of the
oxyhaemoglobin curve, reducing oxygen availability
to the tissues
Respiratory acidosis is caused by CO2 retention due to inadequate pulmonary ventilation (decreased pH, increased pCo2).
Compensatory mechanisms
• increased HCO–
3 by bicarbonate buffer system
• decreased H+ by kidneys (can take several days)
Respiratory acidosis CAUSES (any cause of hypoventilation)
CNS Depression Neuromuscular disease Skeletal disease Artificial ventilation (uncontrolled and unmonitored) Impaired gaseous exchange
Respiratory acidosis CAUSES detailed
CNS Depression • Head injury • Drugs, e.g. opiates, anaesthetics • Coma • Stroke • Encephalitis
Neuromuscular disease
• Myasthenia gravis
• Guillain–Barré syndrome
Skeletal disease
• Kyphoscoliosis
• Ankylosing spondylitis
• Flail chest
Artificial ventilation (uncontrolled and unmonitored)
Impaired gaseous exchange
• Chronic obstructive pulmonary disease
• Alveolar disease, e.g. pneumonia, ARDS (acute respiratory
distress syndrome)
• Thoracic injury, e.g. pulmonary contusions
Respiratory acidosis Sx
anxiety disorientation confusion lethargy somnolence tachycardia bounding arterial pulse cyanosis and hypotension
Respiratory acidosis Dx
■■ ABGs pH <7.35. pCo2 >5.8 kPa. HCO– 3. ■■ CXR Underlying pulmonary disease. ■■ Pulmonary function tests COPD which usually manifests as an obstructive defect (FEV1 , FVC normal). Skeletal disease (reduced chest movement). ■■ EMG and nerve conduction studies Myasthenia gravis and Guillain–Barré syndrome. ■■ CT/MRI head Central (brain stem) lesion.
Beware in Respiratory acidosis
! • Exercise caution when correcting chronic
hypercapnia. Rapid correction of hypercapnia can
alkalinise the CSF causing seizures.
• Associated hypoxaemia secondary to
hypoventilation is the major threat to life and must
be reversed rapidly.
Respiratory alkalosis is a common disorder in critically ill patients.
It occurs when carbon dioxide is lost via excessive pulmonary
ventilation (increased pH, decreased PCO2). Compensatory mechanisms are:
• Decreased HCO–
3 by bicarbonate buffer system
• Increased H+ by kidneys (slow process – may take several days).
Respiratory alkalosis CAUSES (any cause of hyperventilation)
CENTRAL NERVOUS SYSTEM • Pyrexia • Pain • Anxiety • Hysteria • Head injury • Stroke • Encephalitis RESPIRATORY DISORDERS • Pneumonia • Pulmonary oedema • Pulmonary embolus PHYSIOLOGICAL • Pregnancy • High altitude • Severe anaemia DRUGS • Salicylates OTHER CAUSES • Sepsis • Mechanical ventilation • Metabolic acidosis (overcompensation)
Respiratory alkalosis Sx
light headedness
circumoral paraesthesia
dizziness and numbness of the hands and feet
Acute development
of low carbon dioxide levels can occasionally cause cerebral
vasoconstriction leading to confusion, syncope, fits.
Respiratory alkalosis Dx
■■ ABGs pH >7.45. Pco2 <4.4 kPa. Decreased HCO– 3 (compensatory mechanism due to bicarbonate buffer system). ■■ Serum calcium Decreased Ca2+ (due to increased calcium binding to serum albumin). ■■ Serum salicylate level If overdose is suspected. ■■ CT/MRI head Intracranial lesion as a cause of hyperventilation.
Prolonged artificial ventilation with inadequate
monitoring should be remembered as a cause of
respiratory alkalosis.
